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image of Molecular Targets and Nano-Technological Approaches in the Treatment of Hepatic Carcinoma

Abstract

Liver cancer is a leading cause of cancer-related mortality, with about one million people losing their lives each year. The disease becomes even more dangerous when tumors cannot be removed through surgery. Globally, hepatocellular carcinoma (HCC) ranks third in terms of fatality rates among liver cancers. It is also the most frequent type of liver cancer. Due to the high mortality rate associated with this malignancy, it is a hotspot for researchers looking to improve treatment methods. Nanotechnology plays an important part in these attempts. Various types of nanoparticles (NPs) have been investigated for their ability to fight liver cancer. NPs are a vast class of materials. The article details the efforts made to include inorganic NPs, such as silver, gold, metal oxide, platinum, calcium, selenium, and other uncommon materials into drug delivery systems (DDS) for therapeutic, carrier, or imaging purposes. This review discusses the function of carbon-based NPs in DDS for the treatment of liver cancer, including polymeric, polysaccharide, lipid, and carbon dot NPs, all of which have been extensively researched for this purpose. The purpose of this review is to provide a concise overview of recent developments in the field of HCC based on current research and clinical diagnosis and treatment guidelines. Further goals include elucidating the current state of nanomaterials research, its limitations, and the potential for future advancements in the field, as well as the use of nanotechnology in the detection and treatment of HCC.

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2024-10-30
2025-04-13
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References

  1. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  2. Foglia B. Turato C. Cannito S. Hepatocellular Carcinoma: Latest Research in Pathogenesis, Detection and Treatment. Int. J. Mol. Sci. 2023 24 15 12224 10.3390/ijms241512224 37569600
    [Google Scholar]
  3. Huang J. Ngai C.H. Deng Y. Tin M.S. Lok V. Zhang L. Yuan J. Xu W. Zheng Z.J. Wong M.C.S. Cancer Incidence and Mortality in Asian Countries: A Trend Analysis. Cancer Contr. 2022 29 10.1177/10732748221095955 35770775
    [Google Scholar]
  4. Chidambaranathan-Reghupaty S. Fisher P.B. Sarkar D. Hepatocellular carcinoma (HCC): Epidemiology, etiology and molecular classification. Adv. Cancer Res. 2021 149 1 61 10.1016/bs.acr.2020.10.001 33579421
    [Google Scholar]
  5. Shan T. Ran X. Li H. Feng G. Zhang S. Zhang X. Zhang L. Lu L. An L. Fu R. Sun K. Wang S. Chen R. Li L. Chen W. Wei W. Zeng H. He J. Disparities in stage at diagnosis for liver cancer in China. Journal of the National Cancer Center 2023 3 1 7 13 10.1016/j.jncc.2022.12.002 39036312
    [Google Scholar]
  6. Gosalia A.J. Martin P. Jones P.D. Advances and Future Directions in the Treatment of Hepatocellular Carcinoma. Gastroenterol. Hepatol. (N. Y.) 2017 13 7 398 410 28867968
    [Google Scholar]
  7. Laface C. Laforgia M. Molinari P. Ugenti I. Gadaleta C.D. Porta C. Ranieri G. Hepatic Arterial Infusion of Chemotherapy for Advanced Hepatobiliary Cancers: State of the Art. Cancers (Basel) 2021 13 12 3091 10.3390/cancers13123091 34205656
    [Google Scholar]
  8. Rizzo A. Ricci A.D. Brandi G. Trans-Arterial Chemoembolization Plus Systemic Treatments for Hepatocellular Carcinoma: An Update. J. Pers. Med. 2022 12 11 1788 10.3390/jpm12111788 36579504
    [Google Scholar]
  9. Sahin T.K. Rizzo A. Aksoy S. Guven D.C. Prognostic Significance of the Royal Marsden Hospital (RMH) Score in Patients with Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024 16 10 1835 10.3390/cancers16101835 38791914
    [Google Scholar]
  10. Rizzo A. Santoni M. Mollica V. Logullo F. Rosellini M. Marchetti A. Faloppi L. Battelli N. Massari F. Peripheral neuropathy and headache in cancer patients treated with immunotherapy and immuno-oncology combinations: the MOUSEION-02 study. Expert Opin. Drug Metab. Toxicol. 2021 17 12 1455 1466 10.1080/17425255.2021.2029405 35029519
    [Google Scholar]
  11. Muralidhar A. Potluri H.K. Jaiswal T. McNeel D.G. Targeted Radiation and Immune Therapies—Advances and Opportunities for the Treatment of Prostate Cancer. Pharmaceutics 2023 15 1 252 10.3390/pharmaceutics15010252 36678880
    [Google Scholar]
  12. Dash K. Deka P. Bangar S. Chaudhary V. Trif M. Rusu A. Applications of Inorganic Nanoparticles in Food Packaging: A Comprehensive Review. Polymers (Basel) 2022 14 3 521 10.3390/polym14030521 35160510
    [Google Scholar]
  13. Altammar K.A. A review on nanoparticles: characteristics, synthesis, applications, and challenges. Front. Microbiol. 2023 14 1155622 10.3389/fmicb.2023.1155622 37180257
    [Google Scholar]
  14. Anjum S. Ishaque S. Fatima H. Farooq W. Hano C. Abbasi B.H. Anjum I. Emerging Applications of Nanotechnology in Healthcare Systems: Grand Challenges and Perspectives. Pharmaceuticals (Basel) 2021 14 8 707 10.3390/ph14080707 34451803
    [Google Scholar]
  15. Gavas S. Quazi S. Karpiński T.M. Nanoparticles for Cancer Therapy: Current Progress and Challenges. Nanoscale Res. Lett. 2021 16 1 173 10.1186/s11671‑021‑03628‑6 34866166
    [Google Scholar]
  16. Jain K.K. Drug delivery systems-an overview. Drug Deliv. Systems. Springer 2008 1 50 10.1007/978‑1‑59745‑210‑6_1
    [Google Scholar]
  17. Pissuwan D. Niidome T. Cortie M.B. The forthcoming applications of gold nanoparticles in drug and gene delivery systems. J Control Release. 2011 149 1 65 71
    [Google Scholar]
  18. Brannon-Peppas L. Blanchette J.O. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev. 2012 64 206 212 10.1016/j.addr.2012.09.033 15350294
    [Google Scholar]
  19. Velikyan I. Radionuclides for imaging and therapy in oncology. Cancer Theranostics. Elsevier 2014 285 325 10.1016/B978‑0‑12‑407722‑5.00017‑7
    [Google Scholar]
  20. Koirala N. Das D. Fayazzadeh E. Sen S. McClain A. Puskas J.E. Drazba J.A. McLennan G. Folic acid conjugated polymeric drug delivery vehicle for targeted cancer detection in hepatocellular carcinoma. J. Biomed. Mater. Res. A 2019 107 11 2522 2535 10.1002/jbm.a.36758 31334591
    [Google Scholar]
  21. Ramzy L. Nasr M. Metwally A.A. Awad G.A.S. Cancer nanotheranostics: A review of the role of conjugated ligands for overexpressed receptors. Eur. J. Pharm. Sci. 2017 104 273 292 10.1016/j.ejps.2017.04.005 28412485
    [Google Scholar]
  22. Shen Y. Li X. Dong D. Zhang B. Xue Y. Shang P. Transferrin receptor 1 in cancer: a new sight for cancer therapy. Am. J. Cancer Res. 2018 8 6 916 931 30034931
    [Google Scholar]
  23. Zhang J. Zhang M. Ji J. Fang X. Pan X. Wang Y. Wu C. Chen M. Glycyrrhetinic acid-mediated polymeric drug delivery targeting the acidic microenvironment of hepatocellular carcinoma. Pharm. Res. 2015 32 10 3376 3390 10.1007/s11095‑015‑1714‑2 26148773
    [Google Scholar]
  24. Han L. Huang R. Liu S. Huang S. Jiang C. Peptide-conjugated PAMAM for targeted doxorubicin delivery to transferrin receptor overexpressed tumors. Mol. Pharm. 2010 7 6 2156 2165 10.1021/mp100185f 20857964
    [Google Scholar]
  25. Bansal D. Yadav K. Pandey V. Ganeshpurkar A. Agnihotri A. Dubey N. Lactobionic acid coupled liposomes: an innovative strategy for targeting hepatocellular carcinoma. Drug Deliv. 2016 23 1 140 146 10.3109/10717544.2014.907373 24786484
    [Google Scholar]
  26. Xiong Q. Cui M. Bai Y. Liu Y. Liu D. Song T. A supramolecular nanoparticle system based on β-cyclodextrin-conjugated poly-l-lysine and hyaluronic acid for co-delivery of gene and chemotherapy agent targeting hepatocellular carcinoma. Colloids Surf. B Biointerfaces 2017 155 93 103 10.1016/j.colsurfb.2017.04.008 28411478
    [Google Scholar]
  27. Lu C. Rong D. Zhang B. Zheng W. Wang X. Chen Z. Tang W. Current perspectives on the immunosuppressive tumor microenvironment in hepatocellular carcinoma: challenges and opportunities. Mol. Cancer 2019 18 1 130 10.1186/s12943‑019‑1047‑6 31464625
    [Google Scholar]
  28. Kurebayashi Y. Ojima H. Tsujikawa H. Kubota N. Maehara J. Abe Y. Kitago M. Shinoda M. Kitagawa Y. Sakamoto M. Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification. Hepatology 2018 68 3 1025 1041 10.1002/hep.29904 29603348
    [Google Scholar]
  29. Prieto J. Melero I. Sangro B. Immunological landscape and immunotherapy of hepatocellular carcinoma. Nat. Rev. Gastroenterol. Hepatol. 2015 12 12 681 700 10.1038/nrgastro.2015.173 26484443
    [Google Scholar]
  30. Zhou S.L. Zhou Z.J. Hu Z.Q. Huang X.W. Wang Z. Chen E.B. Fan J. Cao Y. Dai Z. Zhou J. Tumorassociated neutrophils recruit macrophages and T-regulatory cells to promote progression of hepatocellular carcinoma and resistance to Sorafenib. Gastroenterology 2016 150 7 1646 1658.e17 10.1053/j.gastro.2016.02.040 26924089
    [Google Scholar]
  31. Quail D.F. Joyce J.A. Microenvironmental regulation of tumor progression and metastasis. Nat. Med. 2013 19 11 1423 1437 10.1038/nm.3394 24202395
    [Google Scholar]
  32. Huang Y Yuan J Righi E Duda DG Fukumura D Poznansky MC Vascular normalization: a strategy to recondition the tumor immune microenvironment. J Immunother Cancer. 2013 1 Suppl 1 P155 10.1186/2051‑1426‑1‑S1‑P155
    [Google Scholar]
  33. Rupaimoole R. Calin G.A. Lopez-Berestein G. Sood A.K. miRNA deregulation in cancer cells and the tumor microenvironment. Cancer Discov. 2016 6 3 235 246 10.1158/2159‑8290.CD‑15‑0893 26865249
    [Google Scholar]
  34. Antsiferova M. Huber M. Meyer M. Piwko-Czuchra A. Ramadan T. MacLeod A.S. Havran W.L. Dummer R. Hohl D. Werner S. Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response. Nat. Commun. 2011 2 1 576 10.1038/ncomms1585 22146395
    [Google Scholar]
  35. McAllister S.S. Weinberg R.A. The tumour-induced systemic environment as a critical regulator of cancer progression and metastasis. Nat. Cell Biol. 2014 16 8 717 727 10.1038/ncb3015 25082194
    [Google Scholar]
  36. Franco O.E. Shaw A.K. Strand D.W. Hayward S.W. Cancer associated fibroblasts in cancer pathogenesis. Semin. Cell Dev. Biol. 2010 21 1 33 39 10.1016/j.semcdb.2009.10.010 19896548
    [Google Scholar]
  37. An Y. Liu F. Chen Y. Yang Q. Crosstalk between cancer‐associated fibroblasts and immune cells in cancer. J. Cell. Mol. Med. 2020 24 1 13 24 10.1111/jcmm.14745 31642585
    [Google Scholar]
  38. Yin Z. Dong C. Jiang K. Xu Z. Li R. Guo K. Shao S. Wang L. Heterogeneity of cancer-associated fibroblasts and roles in the progression, prognosis, and therapy of hepatocellular carcinoma. J. Hematol. Oncol. 2019 12 1 101 10.1186/s13045‑019‑0782‑x 31547836
    [Google Scholar]
  39. Loeffler M. Krüger J.A. Niethammer A.G. Reisfeld R.A. Targeting tumor-associated fibroblasts improves cancer chemotherapy by increasing intratumoral drug uptake. J. Clin. Invest. 2006 116 7 1955 1962 10.1172/JCI26532 16794736
    [Google Scholar]
  40. Singh S. Ross S.R. Acena M. Rowley D.A. Schreiber H. Stroma is critical for preventing or permitting immunological destruction of antigenic cancer cells. J. Exp. Med. 1992 175 1 139 146 10.1084/jem.175.1.139 1309851
    [Google Scholar]
  41. Pisano A. Santolla M.F. De Francesco E.M. De Marco P. Rigiracciolo D.C. Perri M.G. Vivacqua A. Abonante S. Cappello A.R. Dolce V. Belfiore A. Maggiolini M. Lappano R. GPER, IGF‐IR, and EGFR transduction signaling are involved in stimulatory effects of zinc in breast cancer cells and cancer‐associated fibroblasts. Mol. Carcinog. 2017 56 2 580 593 10.1002/mc.22518 27341075
    [Google Scholar]
  42. Hegab A.E. Ozaki M. Kameyama N. Gao J. Kagawa S. Yasuda H. Soejima K. Yin Y. Guzy R.D. Nakamura Y. Ornitz D.M. Betsuyaku T. Effect of FGF/FGFR pathway blocking on lung adenocarcinoma and its cancer‐associated fibroblasts. J. Pathol. 2019 249 2 193 205 10.1002/path.5290 31090071
    [Google Scholar]
  43. Owusu B. Galemmo R. Janetka J. Klampfer L. Hepatocyte growth factor, a key tumor-promoting factor in the tumor microenvironment. Cancers (Basel) 2017 9 4 35 10.3390/cancers9040035 28420162
    [Google Scholar]
  44. Kato T. Noma K. Ohara T. Kashima H. Katsura Y. Sato H. Komoto S. Katsube R. Ninomiya T. Tazawa H. Shirakawa Y. Fujiwara T. Cancerassociated fbroblasts afect intratumoral CD8(+) and FoxP3(+) T cells via IL6 in the tumor microenvironment. Clin. Cancer Res. 2018 24 19 4820 4833 10.1158/1078‑0432.CCR‑18‑0205 29921731
    [Google Scholar]
  45. Hashemi Goradel N. Najafi M. Salehi E. Farhood B. Mortezaee K. Cyclooxygenase‐2 in cancer: A review. J. Cell. Physiol. 2019 234 5 5683 5699 10.1002/jcp.27411 30341914
    [Google Scholar]
  46. Komohara Y. Takeya M. CAFs and TAMs: maestros of the tumour microenvironment. J. Pathol. 2017 241 3 313 315 10.1002/path.4824 27753093
    [Google Scholar]
  47. Bordignon P. Bottoni G. Xu X. Popescu A.S. Truan Z. Guenova E. Kofler L. Jafari P. Ostano P. Röcken M. Neel V. Dotto G.P. Dualism of FGF and TGF-β signaling in heterogeneous cancer-associated fbroblast activation with ETV1 as a critical determinant. Cell Rep. 2019 28 9 2358 2372.e6 10.1016/j.celrep.2019.07.092 31461652
    [Google Scholar]
  48. Kaps L. Schuppan D. Targeting cancer associated fbroblasts in liver fbrosis and liver cancer using nanocarriers. Cells 2020 9 9 2027 10.3390/cells9092027 32899119
    [Google Scholar]
  49. Coll M. Perea L. Boon R. Leite S.B. Vallverdú J. Mannaerts I. Smout A. El Taghdouini A. Blaya D. Rodrigo-Torres D. Graupera I. Aguilar-Bravo B. Chesne C. Najimi M. Sokal E. Lozano J.J. van Grunsven L.A. Verfaillie C.M. Sancho-Bru P. Generation of hepatic stellate cells from human pluripotent stem cells enables in vitro modeling of liver fbrosis. Cell Stem Cell 2018 23 1 101 113.e7 10.1016/j.stem.2018.05.027 30049452
    [Google Scholar]
  50. Barry A.E. Baldeosingh R. Lamm R. Patel K. Zhang K. Dominguez D.A. Kirton K.J. Shah A.P. Dang H. Hepatic stellate cells and hepatocarcinogenesis. Front. Cell Dev. Biol. 2020 8 709 10.3389/fcell.2020.00709 32850829
    [Google Scholar]
  51. Cirri P. Chiarugi P. Cancer-associated-fibroblasts and tumour cells: a diabolic liaison driving cancer progression. Cancer Metastasis Rev. 2012 31 1-2 195 208 10.1007/s10555‑011‑9340‑x 22101652
    [Google Scholar]
  52. Amann T. Bataille F. Spruss T. Mühlbauer M. Gäbele E. Schölmerich J. Kiefer P. Bosserhoff A.K. Hellerbrand C. Activated hepatic stellate cells promote tumorigenicity of hepatocellular carcinoma. Cancer Sci. 2009 100 4 646 653 10.1111/j.1349‑7006.2009.01087.x 19175606
    [Google Scholar]
  53. Zhao W. Zhang L. Xu Y. Zhang Z. Ren G. Tang K. Kuang P. Zhao B. Yin Z. Wang X. Hepatic stellate cells promote tumor progression by enhancement of immunosuppressive cells in an orthotopic liver tumor mouse model. Lab. Invest. 2014 94 2 182 191 10.1038/labinvest.2013.139 24296878
    [Google Scholar]
  54. Yan L. Singh L.S. Zhang L. Xu Y. Role of OGR1 in myeloid-derived cells in prostate cancer. Oncogene 2014 33 2 157 164 10.1038/onc.2012.566 23222714
    [Google Scholar]
  55. Kumar V. Patel S. Tcyganov E. Gabrilovich D.I. The nature of myeloidderived suppressor cells in the tumor microenvironment. Trends Immunol. 2016 37 3 208 220 10.1016/j.it.2016.01.004 26858199
    [Google Scholar]
  56. Zhang F. Hao M. Jin H. Yao Z. Lian N. Wu L. Shao J. Chen A. Zheng S. Canonical hedgehog signalling regulates hepatic stellate cell‐mediated angiogenesis in liver fibrosis. Br. J. Pharmacol. 2017 174 5 409 423 10.1111/bph.13701 28052321
    [Google Scholar]
  57. Höchst B. Schildberg F.A. Sauerborn P. Gäbel Y.A. Gevensleben H. Goltz D. Heukamp L.C. Türler A. Ballmaier M. Gieseke F. Müller I. Kalff J. Kurts C. Knolle P.A. Diehl L. Activated human hepatic stellate cells induce myeloid derived suppressor cells from peripheral blood monocytes in a CD44-dependent fashion. J. Hepatol. 2013 59 3 528 535 10.1016/j.jhep.2013.04.033 23665041
    [Google Scholar]
  58. Mantovani A. Marchesi F. Malesci A. Laghi L. Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat. Rev. Clin. Oncol. 2017 14 7 399 416 10.1038/nrclinonc.2016.217 28117416
    [Google Scholar]
  59. Orecchioni M. Ghosheh Y. Pramod A.B. Ley K. Macrophage polarization: diferent gene signatures in M1(LPS+) vs. classically and M2(LPS-) vs. alternatively activated macrophages. Front. Immunol. 2019 10 1084 10.3389/fimmu.2019.01084 31178859
    [Google Scholar]
  60. Garrido-Martin E.M. Mellows T.W.P. Clarke J. Ganesan A.P. Wood O. Cazaly A. Seumois G. Chee S.J. Alzetani A. King E.V. Hedrick C.C. Thomas G. Friedmann P.S. Ottensmeier C.H. Vijayanand P. Sanchez-Elsner T. M1 hot tumor-associated macrophages boost tissue-resident memory T cells infiltration and survival in human lung cancer. J. Immunother. Cancer 2020 8 2 e000778 10.1136/jitc‑2020‑000778 32699181
    [Google Scholar]
  61. Wang Q. Steger A. Mahner S. Jeschke U. Heidegger H. The formation and therapeutic update of tumor-associated macrophages in cervical cancer. Int. J. Mol. Sci. 2019 20 13 3310 10.3390/ijms20133310 31284453
    [Google Scholar]
  62. Nyiramana M.M. Cho S.B. Kim E.J. Kim M.J. Ryu J.H. Nam H.J. Kim N.G. Park S.H. Choi Y.J. Kang S.S. Jung M. Shin M.K. Han J. Jang I.S. Kang D. Sea hare hydrolysate-induced reduction of human non-small cell lung cancer cell growth through regulation of macrophage polarization and nonapoptotic regulated cell death pathways. Cancers (Basel) 2020 12 3 726 10.3390/cancers12030726 32204484
    [Google Scholar]
  63. Hoves S. Ooi C.H. Wolter C. Sade H. Bissinger S. Schmittnaegel M. Ast O. Giusti A.M. Wartha K. Runza V. Xu W. Kienast Y. Cannarile M.A. Levitsky H. Romagnoli S. De Palma M. Rüttinger D. Ries C.H. Rapid activation of tumor-associated macrophages boosts preexisting tumor immunity. J. Exp. Med. 2018 215 3 859 876 10.1084/jem.20171440 29436396
    [Google Scholar]
  64. Huang Y. Snuderl M. Jain R.K. Polarization of tumor-associated macrophages: a novel strategy for vascular normalization and antitumor immunity. Cancer Cell 2011 19 1 1 2 10.1016/j.ccr.2011.01.005 21251607
    [Google Scholar]
  65. Xia Y. Rao L. Yao H. Wang Z. Ning P. Chen X. Engineering macrophages for cancer immunotherapy and drug delivery. Adv. Mater. 2020 32 40 2002054 10.1002/adma.202002054 32856350
    [Google Scholar]
  66. Yang J.D. Nakamura I. Roberts L.R. The tumor microenvironment in hepatocellular carcinoma: Current status and therapeutic targets. Semin. Cancer Biol. 2011 21 1 35 43 10.1016/j.semcancer.2010.10.007 20946957
    [Google Scholar]
  67. Torimura T. Ueno T. Inuzuka S. Kin M. Ohira H. Kimura Y. Majima Y. Sata M. Abe H. Tanikawa K. The extracellular matrix in hepatocellular carcinoma shows different localization patterns depending on the differentiation and the histological pattern of tumors: immunohistochemical analysis. J. Hepatol. 1994 21 1 37 46 10.1016/S0168‑8278(94)80134‑7 7963419
    [Google Scholar]
  68. Seehawer M. Heinzmann F. D’Artista L. Harbig J. Roux P.F. Hoenicke L. Dang H. Klotz S. Robinson L. Doré G. Rozenblum N. Kang T.W. Chawla R. Buch T. Vucur M. Roth M. Zuber J. Luedde T. Sipos B. Longerich T. Heikenwälder M. Wang X.W. Bischof O. Zender L. Necroptosis microenvironment directs lineage commitment in liver cancer. Nature 2018 562 7725 69 75 10.1038/s41586‑018‑0519‑y 30209397
    [Google Scholar]
  69. Wang H. Zhang C. Chi H. Meng Z. Synergistic anti-hepatoma effect of bufalin combined with sorafenib via mediating the tumor vascular microenvironment by targeting mTOR/VEGF signaling. Int. J. Oncol. 2018 52 6 2051 2060 10.3892/ijo.2018.4351 29620259
    [Google Scholar]
  70. Jing X. Yang F. Shao C. Wei K. Xie M. Shen H. Shu Y. Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol. Cancer 2019 18 1 157 10.1186/s12943‑019‑1089‑9 31711497
    [Google Scholar]
  71. Kudo M. Scientifc rationale for combined Immunotherapy with PD-1/ PD-L1 antibodies and VEGF inhibitors in advanced hepatocellular carcinoma. Cancers (Basel) 2020 12 5 1089 10.3390/cancers12051089 32349374
    [Google Scholar]
  72. Wilson W.R. Hay M.P. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer 2011 11 6 393 410 10.1038/nrc3064 21606941
    [Google Scholar]
  73. Llovet J. Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival. Hepatology 2003 37 2 429 442 10.1053/jhep.2003.50047 12540794
    [Google Scholar]
  74. Rathore P. Rao S.P. Roy A. Satapathy T. Singh V. Jain P. Hepatoprotective activity of isolated herbal compounds. Research. J. Pharm. Technol. 2014 7 2
    [Google Scholar]
  75. Jain A. Jain P. Soni P. Tiwari A. Tiwari S.P. Design and Characterization of Silver Nanoparticles of Different Species of Curcuma in the Treatment of Cancer Using Human Colon Cancer Cell Line (HT-29). J. Gastrointest. Cancer 2023 54 1 90 95 10.1007/s12029‑021‑00788‑7 35043370
    [Google Scholar]
  76. Kasianchuk N. Dobrowolska K. Harkava S. Bretcan A. Zarębska-Michaluk D. Jaroszewicz J. Flisiak R. Rzymski P. Gene-Editing and RNA Interference in Treating Hepatitis B: A Review. Viruses 2023 15 12 2395 10.3390/v15122395 38140636
    [Google Scholar]
  77. Li C. Zhang W. Yang H. Xiang J. Wang X. Wang J. Integrative analysis of dysregulated lncRNA-associated ceRNA network reveals potential lncRNA biomarkers for human hepatocellular carcinoma. PeerJ 2020 8 e8758 10.7717/peerj.8758 32201648
    [Google Scholar]
  78. Singal A.G. Lim J.K. Kanwal F. AGA CLINICAL PRACTICE UPDATE : EXPERT REVIEW AGA Clinical Practice Update on Interaction Between Oral Direct- Hepatocellular Carcinoma : Expert Review. Gastroenterology 2019 156 8 2149 2157 10.1053/j.gastro.2019.02.046 30878469
    [Google Scholar]
  79. Zhang Y. Cui H. Zhang R. Zhang H. Huang W. Nanoparticulation of Prodrug into Medicines for Cancer Therapy. Adv. Sci. (Weinh.) 2021 8 18 2101454 10.1002/advs.202101454 34323373
    [Google Scholar]
  80. Singh R Prasad J Satapathy T Jain P Singh S Pharmacological evaluation for anti-bacterial and anti-inflammatory potential of polymeric microparticles. Indian Journal of Biochemistry and Biophysics 2021 58 2 156 161
    [Google Scholar]
  81. Jin G.Z. Dong H. Yu W.L. Li Y. Lu X.Y. Yu H. Xian Z.H. Dong W. Liu Y.K. Cong W.M. Wu M.C. A novel panel of biomarkers in distinction of small well-differentiated HCC from dysplastic nodules and outcome values. BMC Cancer 2013 13 1 161 10.1186/1471‑2407‑13‑161 23537217
    [Google Scholar]
  82. Patel R. Kuwar U. Dhote N. Alexander A. Nakhate K. Jain P. Ajazuddin Natural Polymers as a Carrier for the Effective Delivery of Antineoplastic Drugs. Curr. Drug Deliv. 2024 21 2 193 210 10.2174/1567201820666230112170035 36644864
    [Google Scholar]
  83. Hagag N.A. A. YBM, A. A. Elsharawy, R. M. Talaat. J. Gastrointest. Cancer 2020 51 234 10.1007/s12029‑019‑00234‑9 31028536
    [Google Scholar]
  84. Mehta N. Dodge J.L. Grab J.D. Yao F.Y. National Experience on Down‐Staging of Hepatocellular Carcinoma Before Liver Transplant: Influence of Tumor Burden, Alpha‐Fetoprotein, and Wait Time. Hepatology 2020 71 3 943 954 10.1002/hep.30879 31344273
    [Google Scholar]
  85. Bhairam M. Prasad J. Verma K. Jain P. Gidwani B. Formulation of transdermal patch of Losartan Potassium & Glipizide for the treatment of hypertension & diabetes. Mater. Today Proc. 2023 83 59 68 [Internet]. 10.1016/j.matpr.2023.01.147
    [Google Scholar]
  86. Dadfar S.M.M. Sekula-Neuner S. Trouillet V. Liu H.Y. Kumar R. Powell A.K. Hirtz M. Evaluation of click chemistry microarrays for immunosensing of alpha-fetoprotein (AFP). Beilstein J. Nanotechnol. 2019 10 2505 2515 10.3762/bjnano.10.241 31921529
    [Google Scholar]
  87. Prasad J. Netam A.K. Satapathy T. Prakash Rao S. Jain P. Anti-hyperlipidemic and Antioxidant Activities of a Combination of Terminalia Arjuna and Commiphora Mukul on Experimental Animals BT. Advances in Biomedical Engineering and Technology Rizvanov A.A. Singh B.K. Ganasala P. Singapore Springer Singapore 2021 175 188
    [Google Scholar]
  88. Poté N. Cauchy F. Albuquerque M. Voitot H. Belghiti J. Castera L. Puy H. Bedossa P. Paradis V. Performance of PIVKA-II for early hepatocellular carcinoma diagnosis and prediction of microvascular invasion. J. Hepatol. 2015 62 4 848 854 10.1016/j.jhep.2014.11.005 25450201
    [Google Scholar]
  89. Stillström D. Beermann M. Engstrand J. Freedman J. Nilsson H. Initial experience with irreversible electroporation of liver tumours. Eur. J. Radiol. Open 2019 6 62 67 10.1016/j.ejro.2019.01.004 30723754
    [Google Scholar]
  90. Zhao Z. Wang X. Zhang Z. Zhang H. Liu H. Zhu X. Li H. Chi X. Yin Z. Gao J. Real-time monitoring of arsenic trioxide release and delivery by activatable T(1) imaging. ACS Nano 2015 9 3 2749 2759 10.1021/nn506640h 25688714
    [Google Scholar]
  91. Sudhir Dhote N. Dineshbhai Patel R. Kuwar U. Agrawal M. Alexander A. Jain P. Application of Thermoresponsive Smart Polymers based in situ Gel as a Novel Carrier for Tumor Targeting [Internet]. Vol. 24. Curr. Cancer Drug Targets 2024 ••• 1 22
    [Google Scholar]
  92. Khatik R. Wang Z. Li F. Zhi D. Kiran S. Dwivedi P. Xu R.X. Liang G. Qiu B. Yang Q. “Magnus nano-bullets” as T1/T2 based dual-modal for in vitro and in vivo MRI visualization. Nanomedicine 2019 15 1 264 273 10.1016/j.nano.2018.10.005
    [Google Scholar]
  93. Rand D. Ortiz V. Liu Y. Derdak Z. Wands J.R. Tatíček M. Rose-Petruck C. Nanomaterials for X-ray imaging: gold nanoparticle enhancement of X-ray scatter imaging of hepatocellular carcinoma. Nano Lett. 2011 11 7 2678 2683 10.1021/nl200858y 21644516
    [Google Scholar]
  94. Jain P. Satapathy T. Pandey R.K. First report on ticks (Acari: Ixodidae) controlling activity of cottonseed oil ( Gossypium Sp.). Int. J. Acarol. 2020 46 4 263 267 [Taylor n Francis]. 10.1080/01647954.2020.1767203
    [Google Scholar]
  95. Song C. Meng X. Liu Y. Shen A. Shao C. Wang K. Cheng H. Fang X. Wang P. Bu W. Susceptibility-weighted imaging for metabolic pathway mapping of low-dosage nanoparticles in organisms. Biomaterials 2020 230 119631 10.1016/j.biomaterials.2019.119631 31761488
    [Google Scholar]
  96. Wei M. Chen S. Li J. Li B. Shen J. Peng Z. Zhou Q. Zou Y. He X. Li S. Li D. Peng B. Lai J. Peng S. Qin B. Kuang M. Prognostic Role of Time to Surgery in Hepatocellular Carcinoma at Barcelona Clinic Liver Cancer Stage 0-A. Ann. Surg. Oncol. 2020 27 10 3740 3753 10.1245/s10434‑020‑08499‑2 32424586
    [Google Scholar]
  97. Netam A.K. Prasad J. Satapathy T. Jain P. Evaluation for Toxicity and Improved Therapeutic Effectiveness of Natural Polymer Co-administered Along with Venocin in Acetic Acid-Induced Colitis Using Rat Model BT. Advances in Biomedical Engineering and Technology Rizvanov A.A. Singh B.K. Ganasala P. Singapore Springer Singapore 2021 207 220
    [Google Scholar]
  98. Tsuda T. Kaibori M. Hishikawa H. Nakatake R. Okumura T. Ozeki E. Hara I. Morimoto Y. Yoshii K. Kon M. PLoS One 2017 12 0183527
    [Google Scholar]
  99. Dai Y.W. Zhu L.X. Zhang Y. Wang S.H. Chen K. Jiang T.T. Xu X.L. Geng X.P. Au@SiO2@CuInS2–ZnS/Anti-AFP fluorescent probe improves HCC cell labeling. Hepatobiliary Pancreat. Dis. Int. 2019 18 3 266 272 10.1016/j.hbpd.2019.03.001 30879890
    [Google Scholar]
  100. Qu Y. Wang Z. Zhao F. Liu J. Zhang W. Li J. Song Z. Xu H. AFM-detected apoptosis of hepatocellular carcinoma cells induced by American ginseng root water extract. Micron 2018 104 1 7 10.1016/j.micron.2017.10.003 29049926
    [Google Scholar]
  101. Sahu B. Comprehensive Review on Non-Alcoholic Fatty Liver Disease (NAFLD). Clinical Advancement and Drug Treatments. Prob. Sci. 2024 1 1 1 7
    [Google Scholar]
  102. Shi H. Gu R. Xu W. Huang H. Xue L. Wang W. Zhang Y. Si W. Dong X. Near-Infrared Light-Harvesting Fullerene-Based Nanoparticles for Promoted Synergetic Tumor Phototheranostics. ACS Appl. Mater. Interfaces 2019 11 48 44970 44977 10.1021/acsami.9b17716 31702130
    [Google Scholar]
  103. Sang M. Han L. Luo R. Qu W. Zheng F. Zhang K. Liu F. Xue J. Liu W. Feng F. CD44 targeted redox-triggered self-assembly with magnetic enhanced EPR effects for effective amplification of gambogic acid to treat triple-negative breast cancer. Biomater. Sci. 2020 8 1 212 223 10.1039/C9BM01171D 31674634
    [Google Scholar]
  104. Kim N. Cheng J. Jung I. Liang J. Shih Y.L. Huang W.Y. Kimura T. L. VHF, Z. C. Zeng, R. Zhenggan, C. S. Kay, S. J. Heo, J. Y. Won, J. Seong. J. Hepatol. 2020 73 121 10.1016/j.jhep.2020.03.005 32165253
    [Google Scholar]
  105. Wang J. Meng J. Ran W. Lee R.J. Teng L. Zhang P. Li Y. Hepatocellular Carcinoma Growth Retardation and PD-1 Blockade Therapy Potentiation with Synthetic High-density Lipoprotein. Nano Lett. 2019 19 8 5266 5276 10.1021/acs.nanolett.9b01717 31361965
    [Google Scholar]
  106. Jain P. Pandey R. Shukla S.S. Natural Sources of Anti-inflammation. Inflammation: Natural Resources and Its Applications. Jain P. Pandey R. Shukla S.S. New Delhi, India Springer 2015 25 133 10.1007/978‑81‑322‑2163‑0_4
    [Google Scholar]
  107. Xue Y. Niu W. Wang M. Chen M. Guo Y. Lei B. Engineering a Biodegradable Multifunctional Antibacterial Bioactive Nanosystem for Enhancing Tumor Photothermo-Chemotherapy and Bone Regeneration. ACS Nano 2020 14 1 442 453 10.1021/acsnano.9b06145 31702885
    [Google Scholar]
  108. Yang Z. Wang J. Liu S. Li X. Miao L. Yang B. Zhang C. He J. Ai S. Guan W. Defeating relapsed and refractory malignancies through a nano-enabled mitochondria-mediated respiratory inhibition and damage pathway. Biomaterials 2020 229 119580 10.1016/j.biomaterials.2019.119580 31707296
    [Google Scholar]
  109. Choi B. Jung H. Yu B. Choi H. Lee J. Kim D.H. Sequential MR Image‐Guided Local Immune Checkpoint Blockade Cancer Immunotherapy Using Ferumoxytol Capped Ultralarge Pore Mesoporous Silica Carriers after Standard Chemotherapy. Small 2019 15 52 1904378 10.1002/smll.201904378
    [Google Scholar]
  110. Xu J. Cheng X. Tan L. Fu C. Ahmed M. Tian J. Dou J. Zhou Q. Ren X. Wu Q. Tang S. Zhou H. Meng X. Yu J. Liang P. Microwave responsive nanoplatform via P-selectin mediated drug delivery for treatment of hepatocellular carcinoma with distant metastasis. Nano Lett. 2019 19 5 2914 2927 10.1021/acs.nanolett.8b05202 30929452
    [Google Scholar]
  111. Han G. Berhane S. Toyoda H. Bettinger D. Elshaarawy O. Chan A.W.H. Kirstein M. Mosconi C. Hucke F. Palmer D. Pinato D.J. Sharma R. Ottaviani D. Jang J.W. Labeur T.A. van Delden O.M. Pirisi M. Stern N. Sangro B. Meyer T. Fateen W. García-Fiñana M. Gomaa A. Waked I. Rewisha E. Aithal G.P. Travis S. Kudo M. Cucchetti A. Peck-Radosavljevic M. Takkenberg R.B. Chan S.L. Vogel A. Johnson P.J. Prediction of survival among patients receiving transarterial chemoembolization for hepatocellular carcinoma: a response-based approach. Hepatology 2019 31698504
    [Google Scholar]
  112. Ebeling Barbier C. Heindryckx F. Lennernäs H. Limitations and Possibilities of Transarterial Chemotherapeutic Treatment of Hepatocellular Carcinoma. Int. J. Mol. Sci. 2021 22 23 13051 10.3390/ijms222313051 34884853
    [Google Scholar]
  113. Sangiovanni A. Prati G.M. Fasani P. Ronchi G. Romeo R. Manini M. Del Ninno E. Morabito A. Colombo M. The natural history of compensated cirrhosis due to hepatitis C virus: A 17-year cohort study of 214 patients. Hepatology 2006 43 6 1303 1310 10.1002/hep.21176 16729298
    [Google Scholar]
  114. Forner A. Llovet J.M. Bruix J. Hepatocellular carcinoma. Lancet 2012 379 9822 1245 1255 10.1016/S0140‑6736(11)61347‑0 22353262
    [Google Scholar]
  115. Xin Q. Ma H. Wang H. Zhang X.D. Tracking tumor heterogeneity and progression with near‐infrared II fluorophores. Exploration 2023 3 2 20220011 10.1002/EXP.20220011 37324032
    [Google Scholar]
  116. Zeng J. Li L. Zhang H. Li J. Liu L. Zhou G. Du Q. Zheng C. Yang X. Radiopaque and uniform alginate microspheres loaded with tantalum nanoparticles for real-time imaging during transcatheter arterial embolization. Theranostics 2018 8 17 4591 4600 10.7150/thno.27379 30279724
    [Google Scholar]
  117. Xu M.X. Ge C.X. Qin Y.T. Gu T.T. Lou D.S. Li Q. Hu L.F. Tan J. Multicombination Approach Suppresses Listeria monocytogenes ‐Induced Septicemia‐Associated Acute Hepatic Failure: The Role of iRhom2 Signaling. Adv. Healthc. Mater. 2018 7 17 1800427 10.1002/adhm.201800427 29944201
    [Google Scholar]
  118. Broutier L. Mastrogiovanni G. Verstegen M.M.A. Francies H.E. Gavarró L.M. Bradshaw C.R. Allen G.E. Arnes-Benito R. Sidorova O. Gaspersz M.P. Georgakopoulos N. Koo B.K. Dietmann S. Davies S.E. Praseedom R.K. Lieshout R. IJzermans J.N.M. Wigmore S.J. Saeb-Parsy K. Garnett M.J. van der Laan L.J.W. Huch M. Human primary liver cancer–derived organoid cultures for disease modeling and drug screening. Nat. Med. 2017 23 12 1424 1435 10.1038/nm.4438 29131160
    [Google Scholar]
  119. Adebayo Michael A.O. Ko S. Tao J. Moghe A. Yang H. Xu M. Russell J.O. Pradhan-Sundd T. Liu S. Singh S. Poddar M. Monga J.S. Liu P. Oertel M. Ranganathan S. Singhi A. Rebouissou S. Zucman-Rossi J. Ribback S. Calvisi D. Qvartskhava N. Görg B. Häussinger D. Chen X. Monga S.P. Inhibiting Glutamine-Dependent mTORC1 Activation Ameliorates Liver Cancers Driven by β-Catenin Mutations. Cell Metab. 2019 29 5 1135 1150.e6 10.1016/j.cmet.2019.01.002 30713111
    [Google Scholar]
  120. Wang T. Zhang J. Hou T. Yin X. Zhang N. Selective targeting of tumor cells and tumor associated macrophages separately by twin-like core–shell nanoparticles for enhanced tumor-localized chemoimmunotherapy. Nanoscale 2019 11 29 13934 13946 10.1039/C9NR03374B 31305839
    [Google Scholar]
  121. Khan M. Zhao P. Khan A. Raza F. Raza S.M. Sarfraz M. Chen Y. Li M. Yang T. Ma X. Xiang G. Synergism of cisplatin-oleanolic acid co-loaded calcium carbonate nanoparticles on hepatocellular carcinoma cells for enhanced apoptosis and reduced hepatotoxicity. Int. J. Nanomedicine 2019 14 3753 3771 10.2147/IJN.S196651 31239661
    [Google Scholar]
  122. Lai I. Swaminathan S. Baylot V. Mosley A. Dhanasekaran R. Gabay M. Felsher D.W. Lipid nanoparticles that deliver IL-12 messenger RNA suppress tumorigenesis in MYC oncogene-driven hepatocellular carcinoma. J. Immunother. Cancer 2018 6 1 125 10.1186/s40425‑018‑0431‑x 30458889
    [Google Scholar]
  123. Zhang Y.Q. Shen Y. Liao M.M. Mao X. Mi G.J. You C. Guo Q.Y. Li W.J. Wang X.Y. Lin N. Webster T.J. Galactosylated chitosan triptolide nanoparticles for overcoming hepatocellular carcinoma: Enhanced therapeutic efficacy, low toxicity, and validated network regulatory mechanisms. Nanomedicine 2019 15 1 86 97 10.1016/j.nano.2018.09.002 30244085
    [Google Scholar]
  124. Callegari E. Guerriero P. Bassi C. D’Abundo L. Frassoldati A. Simoni E. Astolfi L. Silini E.M. Sabbioni S. Negrini M. miR-199a-3p increases the anti-tumor activity of palbociclib in liver cancer models. Mol. Ther. Nucleic Acids 2022 29 538 549 10.1016/j.omtn.2022.07.015 36035756
    [Google Scholar]
  125. Lu J. Wang J. Ling D. Surface Engineering of Nanoparticles for Targeted Delivery to Hepatocellular Carcinoma. Small 2018 14 5 1702037 10.1002/smll.201702037 29251419
    [Google Scholar]
  126. Lu J. Sun J. Li F. Wang J. Liu J. Kim D. Fan C. Hyeon T. Ling D. Highly Sensitive Diagnosis of Small Hepatocellular Carcinoma Using pH-Responsive Iron Oxide Nanocluster Assemblies. J. Am. Chem. Soc. 2018 140 32 10071 10074 10.1021/jacs.8b04169 30059219
    [Google Scholar]
  127. Duclos R.I. Jr Blue K.D. Rufo M.J. Chen X. Guo J.J. Ma X. Lencer W.I. Chinnapen D.J.F. Conjugation of peptides to short-acyl-chain ceramides for delivery across mucosal cell barriers. Bioorg. Med. Chem. Lett. 2020 30 8 127014 10.1016/j.bmcl.2020.127014 32081448
    [Google Scholar]
  128. Hato T. Goyal L. Greten T.F. Duda D.G. Zhu A.X. Immune checkpoint blockade in hepatocellular carcinoma: Current progress and future directions. Hepatology 2014 60 5 1776 1782 10.1002/hep.27246 24912948
    [Google Scholar]
  129. Yau T. Hsu C. Kim T.Y. Choo S.P. Kang Y.K. Hou M.M. Numata K. Yeo W. Chopra A. Ikeda M. Kuromatsu R. Moriguchi M. Chao Y. Zhao H. Anderson J. Cruz C.D. Kudo M. Nivolumab in advanced hepatocellular carcinoma: Sorafenib-experienced Asian cohort analysis. J. Hepatol. 2019 71 3 543 552 10.1016/j.jhep.2019.05.014 31176752
    [Google Scholar]
  130. Seth P.P. Tanowitz M. Bennett C.F. Selective tissue targeting of synthetic nucleic acid drugs. J. Clin. Invest. 2019 129 3 915 925 10.1172/JCI125228 30688661
    [Google Scholar]
  131. Arranja A.G. Pathak V. Lammers T. Shi Y. Tumor-targeted nanomedicines for cancer theranostics. Pharmacol. Res. 2017 115 87 95 10.1016/j.phrs.2016.11.014 27865762
    [Google Scholar]
  132. Stevens N.E. Hatjopolous A. Fraser C.K. Alsharifi M. Diener K.R. Hayball J.D. Preserved antiviral adaptive immunity following polyclonal antibody immunotherapy for severe murine influenza infection. Sci. Rep. 2016 6 1 29154 10.1038/srep29154 27380890
    [Google Scholar]
  133. Goos J.A.C.M. Cho A. Carter L.M. Dilling T.R. Davydova M. Mandleywala K. Puttick S. Gupta A. Price W.S. Quinn J.F. Whittaker M.R. Lewis J.S. Davis T.P. Delivery of polymeric nanostars for molecular imaging and endoradiotherapy through the enhanced permeability and retention (EPR) effect. Theranostics 2020 10 2 567 584 10.7150/thno.36777 31903138
    [Google Scholar]
  134. Su Y. Wang K. Li Y. Song W. Xin Y. Zhao W. Tian J. Ren L. Lu L. Sorafenib-loaded polymeric micelles as passive targeting therapeutic agents for hepatocellular carcinoma therapy. Nanomedicine (Lond.) 2018 13 9 1009 1023 10.2217/nnm‑2018‑0046 29630448
    [Google Scholar]
  135. Zhou J. Han Y. Yang Y. Zhang L. Wang H. Shen Y. Lai J. Chen J. Phospholipid-decorated glycogen nanoparticles for stimuli-responsive drug release and synergetic chemophotothermal therapy of hepatocellular carcinoma. ACS Appl. Mater. Interfaces 2020 12 20 23311 23322 10.1021/acsami.0c02785 32349481
    [Google Scholar]
  136. Elnaggar M.H. Abushouk A.I. Hassan A.H.E. Lamloum H.M. Benmelouka A. Moatamed S.A. Abd-Elmegeed H. Attia S. Samir A. Amr N. Johar D. Zaky S. Nanomedicine as a putative approach for active targeting of hepatocellular carcinoma. Semin. Cancer Biol. 2021 69 91 99 10.1016/j.semcancer.2019.08.016 31421265
    [Google Scholar]
  137. Yoo J. Park C. Yi G. Lee D. Koo H. Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers (Basel) 2019 11 5 640 10.3390/cancers11050640 31072061
    [Google Scholar]
  138. Verslype C. Rosmorduc O. Rougier P. Hepatocellular carcinoma: ESMO–ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2012 23 Suppl. 7 vii41 vii48 10.1093/annonc/mds225 22997453
    [Google Scholar]
  139. Netea-Maier R.T. Smit J.W.A. Netea M.G. Metabolic changes in tumor cells and tumor-associated macrophages: A mutual relationship. Cancer Lett. 2018 413 102 109 10.1016/j.canlet.2017.10.037 29111350
    [Google Scholar]
  140. Campbell R.B. Tumor physiology and delivery of nanopharmaceuticals. Anticancer. Agents Med. Chem. 2006 6 6 503 512 10.2174/187152006778699077 17100555
    [Google Scholar]
  141. Cormode D.P. Skajaa G.O. Delshad A. Parker N. Jarzyna P.A. Calcagno C. Galper M.W. Skajaa T. Briley-Saebo K.C. Bell H.M. Gordon R.E. Fayad Z.A. Woo S.L.C. Mulder W.J.M. A versatile and tunable coating strategy allows control of nanocrystal delivery to cell types in the liver. Bioconjug. Chem. 2011 22 3 353 361 10.1021/bc1003179 21361312
    [Google Scholar]
  142. Dobrovolskaia M.A. Aggarwal P. Hall J.B. McNeil S.E. Preclinical studies to understand nanoparticle interaction with the immune system and its potential effects on nanoparticle biodistribution. Mol. Pharm. 2008 5 4 487 495 10.1021/mp800032f 18510338
    [Google Scholar]
  143. Schipper M.L. Iyer G. Koh A.L. Cheng Z. Ebenstein Y. Aharoni A. Keren S. Bentolila L.A. Li J. Rao J. Chen X. Banin U. Wu A.M. Sinclair R. Weiss S. Gambhir S.S. Particle size, surface coating, and PEGylation influence the biodistribution of quantum dots in living mice. Small 2009 5 1 126 134 10.1002/smll.200800003 19051182
    [Google Scholar]
  144. Chi X. Zhang R. Zhao T. Gong X. Wei R. Yin Z. Lin H. Li D. Shan H. Gao J. Targeted arsenite-loaded magnetic multifunctional nanoparticles for treatment of hepatocellular carcinoma. Nanotechnology 2019 30 17 175101 10.1088/1361‑6528/aaff9e 30654348
    [Google Scholar]
  145. Gullotti E. Park J. Yeo Y. Polydopamine-based surface modification for the development of peritumorally activatable nanoparticles. Pharm. Res. 2013 30 8 1956 1967 10.1007/s11095‑013‑1039‑y 23609560
    [Google Scholar]
  146. Tao W. Zhang J. Zeng X. Liu D. Liu G. Zhu X. Liu Y. Yu Q. Huang L. Mei L. Blended nanoparticle system based on miscible structurally similar polymers: a safe, simple, targeted, and surprisingly high efficiency vehicle for cancer therapy. Adv. Healthc. Mater. 2015 4 8 1203 1214 10.1002/adhm.201400751 25800699
    [Google Scholar]
  147. Lee E.S. Gao Z. Bae Y.H. Recent progress in tumor pH targeting nanotechnology. J. Control. Release 2008 132 3 164 170 10.1016/j.jconrel.2008.05.003 18571265
    [Google Scholar]
  148. Li Z. Zhang H. Han J. Chen Y. Lin H. Yang T. Surface Nanopore Engineering of 2D MXenes for Targeted and Synergistic Multitherapies of Hepatocellular Carcinoma. Adv. Mater. 2018 30 25 1706981 10.1002/adma.201706981 29663543
    [Google Scholar]
  149. Cheng R. Feng F. Meng F. Deng C. Feijen J. Zhong Z. Glutathione-responsive nano-vehicles as a promising platform for targeted intracellular drug and gene delivery. J. Control. Release 2011 152 1 2 12 10.1016/j.jconrel.2011.01.030 21295087
    [Google Scholar]
  150. Saeed A.O. Newland B. Pandit A. Wang W. The reverse of polymer degradation: in situ crosslinked gel formation through disulfide cleavage. Chem. Commun. (Camb.) 2012 48 4 585 587 10.1039/C1CC16538K 22113516
    [Google Scholar]
  151. Li Z. Han J. Yu L. Qian X. Xing H. Lin H. Wu M. Yang T. Chen Y. Synergistic sonodynamic/ chemotherapeutic suppression of hepatocellular carcinoma by targeted biodegradable mesoporous nanosonosensitizers. Adv. Funct. Mater. 2018 28 26 1800145 10.1002/adfm.201800145
    [Google Scholar]
  152. Milosevic M. Fyles A. Hedley D. Hill R. The human tumor microenvironment: invasive (needle) measurement of oxygen and interstitial fluid pressure. Semin. Radiat. Oncol. 2004 14 3 249 258 10.1016/j.semradonc.2004.04.006 15254868
    [Google Scholar]
  153. Khawar I.A. Kim J.H. Kuh H.J. Improving drug delivery to solid tumors: Priming the tumor microenvironment. J. Control. Release 2015 201 78 89 10.1016/j.jconrel.2014.12.018 25526702
    [Google Scholar]
  154. Chen B. Dai W. Mei D. Liu T. Li S. He B. He B. Yuan L. Zhang H. Wang X. Zhang Q. Comprehensively priming the tumor microenvironment by cancer-associated fibroblast-targeted liposomes for combined therapy with cancer cell-targeted chemotherapeutic drug delivery system. J. Control. Release 2016 241 68 80 10.1016/j.jconrel.2016.09.014 27641831
    [Google Scholar]
  155. Perche F. Biswas S. Wang T. Zhu L. Torchilin V.P. Hypoxia‐Targeted siRNA Delivery. Angew. Chem. Int. Ed. 2014 53 13 3362 3366 10.1002/anie.201308368 24554550
    [Google Scholar]
  156. Wu B. Shang H. Liang X. Sun Y. Jing H. Han X. Cheng W. Preparation of novel targeting nanobubbles conjugated with small interfering RNA for concurrent molecular imaging and gene therapy in vivo. FASEB J. 2019 33 12 14129 14136 10.1096/fj.201900716RR 31657628
    [Google Scholar]
  157. Liu Z. Zhang J. Tian Y. Zhang L. Han X. Wang Q. Cheng W. Targeted delivery of reduced graphene oxide nanosheets using multifunctional ultrasound nanobubbles for visualization and enhanced photothermal therapy. Int. J. Nanomedicine 2018 13 7859 7872 10.2147/IJN.S181268 30538464
    [Google Scholar]
  158. Wang R. Luo Y. Yang S. Lin J. Gao D. Zhao Y. Liu J. Shi X. Wang X. Hyaluronic acid-modified manganese-chelated dendrimer-entrapped gold nanoparticles for the targeted CT/MR dual-mode imaging of hepatocellular carcinoma. Sci. Rep. 2016 6 1 33844 10.1038/srep33844 27653258
    [Google Scholar]
  159. Shen J.M. Li X.X. Fan L.L. Zhou X. Han J.M. Jia M.K. Wu L.F. Zhang X.X. Chen J. Heterogeneous dimer peptide-conjugated polylysine dendrimer-Fe3O4 composite as a novel nanoscale molecular probe for early diagnosis and therapy in hepatocellular carcinoma. Int. J. Nanomedicine 2017 12 1183 1200 10.2147/IJN.S126887 28243083
    [Google Scholar]
  160. Mintz K. Waidely E. Zhou Y. Peng Z. Al-Youbi A.O. Bashammakh A.S. El-Shahawi M.S. Leblanc R.M. Carbon dots and gold nanoparticles based immunoassay for detection of alpha-L-fucosidase. Anal. Chim. Acta 2018 1041 114 121 10.1016/j.aca.2018.08.055 30340683
    [Google Scholar]
  161. Zhang N. Lu C. Shu G. Li J. Chen M. Chen C. Lv X. Xu X. Weng W. Weng Q. Tang B. Du Y.Z. Ji J. Gadolinium-loaded calcium phosphate nanoparticles for magnetic resonance imaging of orthotopic hepatocarcinoma and primary hepatocellular carcinoma. Biomater. Sci. 2020 8 7 1961 1972 10.1039/C9BM01544B 32064471
    [Google Scholar]
  162. Wang Z. Chang Z. Lu M. Shao D. Yue J. Yang D. Zheng X. Li M. He K. Zhang M. Chen L. Dong W. Shape-controlled magnetic mesoporous silica nanoparticles for magnetically-mediated suicide gene therapy of hepatocellular carcinoma. Biomaterials 2018 154 147 157 10.1016/j.biomaterials.2017.10.047 29128843
    [Google Scholar]
  163. Wang J. Zhou Y. Guo S. Wang Y. Nie C. Wang H. Wang J. Zhao Y. Li X. Chen X. Cetuximab conjugated and doxorubicin loaded silica nanoparticles for tumor-targeting and tumor microenvironment responsive binary drug delivery of liver cancer therapy. Mater. Sci. Eng. C 2017 76 944 950 10.1016/j.msec.2017.03.131 28482611
    [Google Scholar]
  164. Wu D. Yu Y. Jin D. Xiao M.M. Zhang Z.Y. Zhang G.J. Dual-aptamer modifed graphene feld-efect transistor nanosensor for label-free and specifc detection of hepatocellular carcinoma-derived microvesicles. Anal. Chem. 2020 92 5 4006 4015 10.1021/acs.analchem.9b05531 32040907
    [Google Scholar]
  165. Wu C. Li P. Fan N. Han J. Zhang W. Zhang W. Tang B. A dual-targeting functionalized graphene flm for rapid and highly sensitive fuorescence imaging detection of hepatocellular carcinoma circulating tumor cells. ACS Appl. Mater. Interfaces 2019 11 48 44999 45006 10.1021/acsami.9b18410 31714050
    [Google Scholar]
  166. Ma X. Jin Y. Wang Y. Zhang S. Peng D. Yang X. Wei S. Chai W. Li X. Tian J. Multimodality molecular imaging-guided tumor border delineation and photothermal therapy analysis based on graphene oxide-conjugated gold nanoparticles chelated with Gd. Contrast Media Mol. Imaging 2018 2018 1 14 10.1155/2018/9321862 29853812
    [Google Scholar]
  167. Liu F. Li X. Li Y. Qi Y. Yuan H. He J. Li W. Zhou M. Designing pH-triggered drug release iron oxide nanocomposites for MRI-guided photothermal-chemoembolization therapy of liver orthotopic cancer. Biomater. Sci. 2019 7 5 1842 1851 10.1039/C9BM00056A 30942214
    [Google Scholar]
  168. Xu Y.H. Yang J. Meng J. Wang H. Targeted MR imaging adopting T1-weighted ultra-small iron oxide nanoparticles for early hepatocellular carcinoma: an in vitro and in vivo study. Chin. Med. Sci. J. 2020 35 2 142 150 32684234
    [Google Scholar]
  169. Siciliano G. Corricelli M. Iacobazzi R.M. Canepa F. Comegna D. Fanizza E. Del Gatto A. Saviano M. Laquintana V. Comparelli R. Mascolo G. Murgolo S. Striccoli M. Agostiano A. Denora N. Zaccaro L. Curri M.L. Depalo N. Gold-speckled SPION@SiO(2) nanoparticles decorated with thiocarbohydrates for ASGPR1 targeting: towards HCC dual mode imaging potential applications. Chemistry 2020 26 48 11048 11059 10.1002/chem.202002142 32628283
    [Google Scholar]
  170. Fukuda K. Mori K. Hasegawa N. Nasu K. Ishige K. Okamoto Y. Shiigai M. Abei M. Minami M. Hyodo I. Safety margin of radiofrequency ablation for hepatocellular carcinoma: a prospective study using magnetic resonance imaging with superparamagnetic iron oxide. Jpn. J. Radiol. 2019 37 7 555 563 10.1007/s11604‑019‑00843‑1 31102138
    [Google Scholar]
  171. Zhang H. Deng L. Liu H. Mai S. Cheng Z. Shi G. Zeng H. Wu Z. Enhanced fluorescence/magnetic resonance dual imaging and gene therapy of liver cancer using cationized amylose nanoprobe. Mater. Today Bio 2022 13 100220 10.1016/j.mtbio.2022.100220 35243295
    [Google Scholar]
  172. Liu Y. Li J. Liu F. Zhang L. Feng L. Yu D. Zhang N. Theranostic polymeric micelles for the diagnosis and treatment of hepatocellular carcinoma. J. Biomed. Nanotechnol. 2015 11 4 613 622 10.1166/jbn.2015.1945 26310068
    [Google Scholar]
  173. Han Y. An Y. Jia G. Wang X. He C. Ding Y. Tang Q. Theranostic micelles based on upconversion nanoparticles for dual-modality imaging and photodynamic therapy in hepatocellular carcinoma. Nanoscale 2018 10 14 6511 6523 10.1039/C7NR09717D 29569668
    [Google Scholar]
  174. Zhao H. Wu M. Zhu L. Tian Y. Wu M. Li Y. Deng L. Jiang W. Shen W. Wang Z. Mei Z. Li P. Ran H. Zhou Z. Ren J. Cell-penetrating peptide-modifed targeted drug-loaded phase-transformation lipid nanoparticles combined with low-intensity focused ultrasound for precision theranostics against hepatocellular carcinoma. Theranostics 2018 8 7 1892 1910 10.7150/thno.22386 29556363
    [Google Scholar]
  175. Li H. Shi S. Wu M. Shen W. Ren J. Mei Z. Ran H. Wang Z. Tian Y. Gao J. Zhao H. iRGD peptide-mediated liposomal nanoparticles with photoacoustic/ultrasound dual-modality imaging for precision theranostics against hepatocellular carcinoma. Int. J. Nanomedicine 2021 16 6455 6475 10.2147/IJN.S325891 34584411
    [Google Scholar]
  176. Liu J. Ren L. Li S. Li W. Zheng X. Yang Y. Fu W. Yi J. Wang J. Du G. The biology, function, and applications of exosomes in cancer. Acta Pharm. Sin. B 2021 11 9 2783 2797 10.1016/j.apsb.2021.01.001 34589397
    [Google Scholar]
  177. Liu Y. Chen Z. Liu C. Yu D. Lu Z. Zhang N. Gadolinium-loaded polymeric nanoparticles modified with Anti-VEGF as multifunctional MRI contrast agents for the diagnosis of liver cancer. Biomaterials 2011 32 22 5167 5176 10.1016/j.biomaterials.2011.03.077 21521627
    [Google Scholar]
  178. Shi Z. Chu C. Zhang Y. Su Z. Lin H. Pang X. Wang X. Liu G. Li W. Self-assembled metalorganic nanoparticles for multimodal imaging-guided photothermal therapy of hepatocellular carcinoma. J. Biomed. Nanotechnol. 2018 14 11 1934 1943 10.1166/jbn.2018.2636 30165929
    [Google Scholar]
  179. Najahi-Missaoui W. Arnold R.D. Safe nanoparticles: are we there yet? IJMS 2020
    [Google Scholar]
  180. Pan L. Liu J. He Q. Shi J. MSN-mediated sequential vascular-to-cell nuclear-targeted drug delivery for efficient tumor regression. Adv. Mater. 2014 26 39 6742 6748 10.1002/adma.201402752 25159109
    [Google Scholar]
  181. Liu X. Sun Y. Xu S. Gao X. Kong F. Xu K. Tang B. Homotypic cell membranecloaked biomimetic nanocarrier for the targeted chemotherapy of hepatocellular carcinoma. Theranostics 2019 9 20 5828 5838 10.7150/thno.34837 31534522
    [Google Scholar]
  182. Liang Y.J. Yu H. Feng G. Zhuang L. Xi W. Ma M. Chen J. Gu N. Zhang Y. High-performance poly(lactic-co-glycolic acid)-magnetic microspheres prepared by rotating membrane emulsifcation for transcatheter arterial embolization and magnetic ablation in VX(2) liver tumors. ACS Appl. Mater. Interfaces 2017 9 50 43478 43489 10.1021/acsami.7b14330 29116741
    [Google Scholar]
  183. Mondal J. Khuda-Bukhsh A.R. Cisplatin and farnesol co-encapsulated PLGA nano-particles demonstrate enhanced anti-cancer potential against hepatocellular carcinoma cells in vitro. Mol. Biol. Rep. 2020 47 5 3615 3628 10.1007/s11033‑020‑05455‑x 32314187
    [Google Scholar]
  184. Yao Q. Dai Z. Hoon Choi J. Kim D. Zhu L. Building stable MMP2-responsive multifunctional polymeric micelles by an all-in-one polymer-lipid conjugate for tumor-targeted intracellular drug delivery. ACS Appl. Mater. Interfaces 2017 9 38 32520 32533 10.1021/acsami.7b09511 28870072
    [Google Scholar]
  185. Jin X. Sun P. Tong G. Zhu X. Star polymer-based unimolecular micelles and their application in bio-imaging and diagnosis. Biomaterials 2018 178 738 750 10.1016/j.biomaterials.2018.01.051 29429845
    [Google Scholar]
  186. Zhuang W. Xu Y. Li G. Hu J. Ma B. Yu T. Su X. Wang Y. Redox and pH dual-responsive polymeric micelles with aggregation-induced emission feature for cellular imaging and chemotherapy. ACS Appl. Mater. Interfaces 2018 10 22 18489 18498 10.1021/acsami.8b02890 29737837
    [Google Scholar]
  187. Ding Y. Xu H. Xu C. Tong Z. Zhang S. Bai Y. Chen Y. Xu Q. Zhou L. Ding H. Sun Z. Yan S. Mao Z. Wang W. A nanomedicine fabricated from gold nanoparticles-decorated metal-organic framework for cascade chemo/chemodynamic cancer therapy. Adv. Sci. (Weinh.) 2020 7 17 2001060 10.1002/advs.202001060 32995124
    [Google Scholar]
  188. Kalluri R. The biology and function of exosomes in cancer. J. Clin. Invest. 2016 126 4 1208 1215 10.1172/JCI81135 27035812
    [Google Scholar]
  189. Li C. Xu X. Biological functions and clinical applications of exosomal non-coding RNAs in hepatocellular carcinoma. Cell. Mol. Life Sci. 2019 76 21 4203 4219 10.1007/s00018‑019‑03215‑0 31300868
    [Google Scholar]
  190. Cocucci E. Meldolesi J. Ectosomes and exosomes: shedding the confusion between extracellular vesicles. Trends Cell Biol. 2015 25 6 364 372 10.1016/j.tcb.2015.01.004 25683921
    [Google Scholar]
  191. Rios-Colon L. Arthur E. Niture S. Qi Q. Moore J.T. Kumar D. The role of exosomes in the crosstalk between adipocytes and liver cancer cells. Cells 2020 9 9 1988 10.3390/cells9091988 32872417
    [Google Scholar]
  192. Wu Q. Zhou L. Lv D. Zhu X. Tang H. Exosome-mediated communication in the tumor microenvironment contributes to hepatocellular carcinoma development and progression. J. Hematol. Oncol. 2019 12 1 53 10.1186/s13045‑019‑0739‑0 31142326
    [Google Scholar]
  193. Abudoureyimu M. Zhou H. Zhi Y. Wang T. Feng B. Wang R. Chu X. Recent progress in the emerging role of exosome in hepatocellular carcinoma. Cell Prolif. 2019 52 2 e12541 10.1111/cpr.12541 30397975
    [Google Scholar]
  194. He R. Wang Z. Shi W. Yu L. Xia H. Huang Z. Liu S. Zhao X. Xu Y. Yam J.W.P. Cui Y. Exosomes in hepatocellular carcinoma microenvironment and their potential clinical application value. Biomed. Pharmacother. 2021 138 111529 10.1016/j.biopha.2021.111529 34311529
    [Google Scholar]
  195. Ge Y. Mu W. Ba Q. Li J. Jiang Y. Xia Q. Wang H. Hepatocellular carcinoma-derived exosomes in organotropic metastasis, recurrence and early diagnosis application. Cancer Lett. 2020 477 41 48 10.1016/j.canlet.2020.02.003 32112905
    [Google Scholar]
  196. Loh X.J. Lee T.C. Dou Q. Deen G.R. Utilising inorganic nanocarriers for gene delivery. Biomater. Sci. 2016 4 1 70 86 10.1039/C5BM00277J 26484365
    [Google Scholar]
  197. Thomas M. Klibanov A.M. Non-viral gene therapy: polycation-mediated DNA delivery. Appl. Microbiol. Biotechnol. 2003 62 1 27 34 10.1007/s00253‑003‑1321‑8 12719940
    [Google Scholar]
  198. Elahi N. Kamali M. Baghersad M.H. Recent biomedical applications of gold nanoparticles: A review. Talanta 2018 184 537 556 10.1016/j.talanta.2018.02.088 29674080
    [Google Scholar]
  199. Li N. Zhao P. Astruc D. Anisotropic gold nanoparticles: synthesis, properties, applications, and toxicity. Angew. Chem. Int. Ed. 2014 53 7 1756 1789 10.1002/anie.201300441 24421264
    [Google Scholar]
  200. Yeh Y.C. Creran B. Rotello V.M. Gold nanoparticles: preparation, properties, and applications in bionanotechnology. Nanoscale 2012 4 6 1871 1880 10.1039/C1NR11188D 22076024
    [Google Scholar]
  201. Zeng S. Yong K.T. Roy I. Dinh X.Q. Yu X. Luan F. A review on functionalized gold nanoparticles for biosensing applications. Plasmonics 2011 6 3 491 506 10.1007/s11468‑011‑9228‑1
    [Google Scholar]
  202. Norouzi H. Khoshgard K. Akbarzadeh F. In vitro outlook of gold nanoparticles in photo-thermal therapy: a literature review. Lasers Med. Sci. 2018 33 4 917 926 10.1007/s10103‑018‑2467‑z 29492712
    [Google Scholar]
  203. Haume K. Rosa S. Grellet S. Śmiałek M.A. Butterworth K.T. Solov’yov A.V. Prise K.M. Golding J. Mason N.J. Gold nanoparticles for cancer radiotherapy: a review. Cancer Nanotechnol. 2016 7 1 8 27 10.1186/s12645‑016‑0021‑x 27867425
    [Google Scholar]
  204. Chang Y. Yan W. He X. Zhang L. Li C. Huang H. Nace G. Geller D.A. Lin J. Tsung A. miR-375 inhibits autophagy and reduces viability of hepatocellular carcinoma cells under hypoxic conditions. Gastroenterology 2012 143 1 177 187.e8 10.1053/j.gastro.2012.04.009 22504094
    [Google Scholar]
  205. Asharani P.V. lianwu Y. Gong Z. Valiyaveettil S. Comparison of the toxicity of silver, gold and platinum nanoparticles in developing zebrafish embryos. Nanotoxicology 2011 5 1 43 54 10.3109/17435390.2010.489207 21417687
    [Google Scholar]
  206. Stepanov A. Golubev A. Nikitin S. Osin Y. A review on the fabrication and properties of platinum nanoparticles. Rev. Adv. Mater. Sci. 2014 38 2 160 175
    [Google Scholar]
  207. Jaganathan A. Murugan K. Panneerselvam C. Madhiyazhagan P. Dinesh D. Vadivalagan C. Aziz A.T. Chandramohan B. Suresh U. Rajaganesh R. Subramaniam J. Nicoletti M. Higuchi A. Alarfaj A.A. Munusamy M.A. Kumar S. Benelli G. Earthworm-mediated synthesis of silver nanoparticles: A potent tool against hepatocellular carcinoma, Plasmodium falciparum parasites and malaria mosquitoes. Parasitol. Int. 2016 65 3 276 284 10.1016/j.parint.2016.02.003 26873539
    [Google Scholar]
  208. Saratale R.G. Shin H.S. Kumar G. Benelli G. Kim D.S. Saratale G.D. Exploiting antidiabetic activity of silver nanoparticles synthesized using Punica granatum leaves and anticancer potential against human liver cancer cells (HepG2). Artif. Cells Nanomed. Biotechnol. 2018 46 1 211 222 10.1080/21691401.2017.1337031 28612655
    [Google Scholar]
  209. Karimzadeh K. Elham sharifi Bakhshi N. Ramzanpoor M. Biogenic silver nanoparticles using Oxalis corniculata characterization and their clinical implications. J. Drug Deliv. Sci. Technol. 2019 54 101263 101278 10.1016/j.jddst.2019.101263
    [Google Scholar]
  210. Ahmadian E. Dizaj S.M. Rahimpour E. Hasanzadeh A. Eftekhari A. Hosain zadegan H. Halajzadeh J. Ahmadian H. Effect of silver nanoparticles in the induction of apoptosis on human hepatocellular carcinoma (HepG2) cell line. Mater. Sci. Eng. C 2018 93 465 471 10.1016/j.msec.2018.08.027 30274079
    [Google Scholar]
  211. Shoshan M.S. Vonderach T. Hattendorf B. Wennemers H. Peptide-coated platinum nanoparticles with selective toxicity against liver cancer cells. Angew. Chem. Int. Ed. 2019 58 15 4901 4905 10.1002/anie.201813149 30561882
    [Google Scholar]
  212. George J.M. Antony A. Mathew B. Metal oxide nanoparticles in electrochemical sensing and biosensing: a review. Mikrochim. Acta 2018 185 7 358 383 10.1007/s00604‑018‑2894‑3 29974265
    [Google Scholar]
  213. Sarkar A. Ghosh M. Sil P.C. Nanotoxicity: oxidative stress mediated toxicity of metal and metal oxide nanoparticles. J. Nanosci. Nanotechnol. 2014 14 1 730 743 10.1166/jnn.2014.8752 24730293
    [Google Scholar]
  214. Laurent S. Forge D. Port M. Roch A. Robic C. Vander Elst L. Muller R.N. Magnetic iron oxide nanoparticles: synthesis, stabilization, vectorization, physicochemical characterizations, and biological applications. Chem. Rev. 2008 108 6 2064 2110 10.1021/cr068445e 18543879
    [Google Scholar]
  215. Wahajuddin S.A. Arora S. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers. Int. J. Nanomedicine 2012 7 3445 3471 10.2147/IJN.S30320 22848170
    [Google Scholar]
  216. Laurent S. Dutz S. Häfeli U.O. Mahmoudi M. Magnetic fluid hyperthermia: Focus on superparamagnetic iron oxide nanoparticles. Adv. Colloid Interface Sci. 2011 166 1-2 8 23 10.1016/j.cis.2011.04.003 21601820
    [Google Scholar]
  217. Maeng J.H. Lee D.H. Jung K.H. Bae Y.H. Park I.S. Jeong S. Jeon Y.S. Shim C.K. Kim W. Kim J. Lee J. Lee Y.M. Kim J.H. Kim W.H. Hong S.S. Multifunctional doxorubicin loaded superparamagnetic iron oxide nanoparticles for chemotherapy and magnetic resonance imaging in liver cancer. Biomaterials 2010 31 18 4995 5006 10.1016/j.biomaterials.2010.02.068 20347138
    [Google Scholar]
  218. Depalo N. Iacobazzi R.M. Valente G. Arduino I. Villa S. Canepa F. Laquintana V. Fanizza E. Striccoli M. Cutrignelli A. Lopedota A. Porcelli L. Azzariti A. Franco M. Curri M.L. Denora N. Sorafenib delivery nanoplatform based on superparamagnetic iron oxide nanoparticles magnetically targets hepatocellular carcinoma. Nano Res. 2017 10 7 2431 2448 10.1007/s12274‑017‑1444‑3
    [Google Scholar]
  219. Kandasamy G. Sudame A. Luthra T. Saini K. Maity D. Functionalized hydrophilic superparamagnetic iron oxide nanoparticles for magnetic fluid hyperthermia application in liver cancer treatment. ACS Omega 2018 3 4 3991 4005 10.1021/acsomega.8b00207 30023884
    [Google Scholar]
  220. Zhao P. Li M. Wang Y. Chen Y. He C. Zhang X. Yang T. Lu Y. You J. Lee R.J. Xiang G. Enhancing anti-tumor efficiency in hepatocellular carcinoma through the autophagy inhibition by miR-375/sorafenib in lipid-coated calcium carbonate nanoparticles. Acta Biomater. 2018 72 248 255 10.1016/j.actbio.2018.03.022 29555460
    [Google Scholar]
  221. Zhao P. Wu S. Cheng Y. You J. Chen Y. Li M. He C. Zhang X. Yang T. Lu Y. Lee R.J. He X. Xiang G. MiR-375 delivered by lipid-coated doxorubicin-calcium carbonate nanoparticles overcomes chemoresistance in hepatocellular carcinoma. Nanomedicine 2017 13 8 2507 2516 10.1016/j.nano.2017.05.010 28577837
    [Google Scholar]
  222. Wu J.Y. Wang Z. Zhang G. Lu X. Qiang G.H. Hu W. Ji A.L. Wu J.H. Jiang C.P. Targeted co-delivery of Beclin 1 siRNA and FTY720 to hepatocellular carcinoma by calcium phosphate nanoparticles for enhanced anticancer efficacy. Int. J. Nanomedicine 2018 13 1265 1280 10.2147/IJN.S156328 29551896
    [Google Scholar]
  223. Bauer I.W. Li S.P. Han Y.C. Yuan L. Yin M.Z. Internalization of hydroxyapatite nanoparticles in liver cancer cells. J. Mater. Sci. Mater. Med. 2008 19 3 1091 1095 10.1007/s10856‑007‑3124‑4 17701307
    [Google Scholar]
  224. Yanhua W. Hao H. Li Y. Zhang S. Selenium-substituted hydroxyapatite nanoparticles and their in vivo antitumor effect on hepatocellular carcinoma. Colloids Surf. B Biointerfaces 2016 140 297 306 10.1016/j.colsurfb.2015.12.056 26764116
    [Google Scholar]
  225. Fang X. Wu X. Li C. Zhou B. Chen X. Chen T. Yang F. Targeting selenium nanoparticles combined with baicalin to treat HBV-infected liver cancer. RSC Advances 2017 7 14 8178 8185 10.1039/C6RA28229F
    [Google Scholar]
  226. Xia Y. Zhong J. Zhao M. Tang Y. Han N. Hua L. Xu T. Wang C. Zhu B. Galactose-modified selenium nanoparticles for targeted delivery of doxorubicin to hepatocellular carcinoma. Drug Deliv. 2019 26 1 1 11 10.1080/10717544.2018.1556359 31928356
    [Google Scholar]
  227. Merget R. Bauer T. Küpper H. Philippou S. Bauer H. Breitstadt R. Bruening T. Health hazards due to the inhalation of amorphous silica. Arch. Toxicol. 2002 75 11-12 625 634 10.1007/s002040100266 11876495
    [Google Scholar]
  228. Meyer A. Sandler D.P. Beane Freeman L.E. Hofmann J.N. Parks C.G. Pesticide exposure and risk of rheumatoid arthritis among licensed male pesticide applicators in the agricultural health study. Environ. Health Perspect. 2017 125 7 077010 077016 10.1289/EHP1013 28718769
    [Google Scholar]
  229. Wu S.H. Mou C.Y. Lin H.P. Synthesis of mesoporous silica nanoparticles. Chem. Soc. Rev. 2013 42 9 3862 3875 10.1039/c3cs35405a 23403864
    [Google Scholar]
  230. Liao Y-T. Liu C-H. Yu J. Wu K.C. Liver cancer cells: targeting and prolonged-release drug carriers consisting of mesoporous silica nanoparticles and alginate microspheres. Int. J. Nanomedicine 2014 9 2767 2778 24940057
    [Google Scholar]
  231. Li T. Chen X. Liu Y. Fan L. Lin L. Xu Y. Chen S. Shao J. pH-Sensitive mesoporous silica nanoparticles anticancer prodrugs for sustained release of ursolic acid and the enhanced anti-cancer efficacy for hepatocellular carcinoma cancer. Eur. J. Pharm. Sci. 2017 96 456 463 10.1016/j.ejps.2016.10.019 27771513
    [Google Scholar]
  232. Lv Y. Li J. Chen H. Bai Y. Zhang L. Glycyrrhetinic acid-functionalized mesoporous silica nanoparticles as hepatocellular carcinoma-targeted drug carrier. Int. J. Nanomedicine 2017 12 4361 4370 10.2147/IJN.S135626 28652738
    [Google Scholar]
  233. Xue H. Yu Z. Liu Y. Yuan W. Yang T. You J. He X. Lee R.J. Li L. Xu C. Delivery of miR-375 and doxorubicin hydrochloride by lipid-coated hollow mesoporous silica nanoparticles to overcome multiple drug resistance in hepatocellular carcinoma. Int. J. Nanomedicine 2017 12 5271 5287 10.2147/IJN.S135306 28769563
    [Google Scholar]
  234. Rahman M. Almalki W.H. Alrobaian M. Iqbal J. Alghamdi S. Alharbi K.S. Alruwaili N.K. Hafeez A. Shaharyar A. Singh T. Waris M. Kumar V. Beg S. Nanocarriers-loaded with natural actives as newer therapeutic interventions for treatment of hepatocellular carcinoma. Expert Opin. Drug Deliv. 2021 18 4 489 513 10.1080/17425247.2021.1854223 33225771
    [Google Scholar]
  235. Delgado C. Francis G.E. Fisher D. The uses and properties of PEG-linked proteins. Crit. Rev. Ther. Drug Carrier Syst. 1992 9 3-4 249 304 1458545
    [Google Scholar]
  236. Karakoti A.S. Das S. Thevuthasan S. Seal S. PEGylated inorganic nanoparticles. Angew. Chem. Int. Ed. 2011 50 9 1980 1994 10.1002/anie.201002969 21275011
    [Google Scholar]
  237. Ghitman J. Biru E.I. Stan R. Iovu H. Review of hybrid PLGA nanoparticles: Future of smart drug delivery and theranostics medicine. Mater. Des. 2020 193 108805 108824 10.1016/j.matdes.2020.108805
    [Google Scholar]
  238. Wu B. Liang Y. Tan Y. Xie C. Shen J. Zhang M. Liu X. Yang L. Zhang F. Liu L. Cai S. Huai D. Zheng D. Zhang R. Zhang C. Chen K. Tang X. Sui X. Genistein-loaded nanoparticles of star-shaped diblock copolymer mannitol-core PLGA–TPGS for the treatment of liver cancer. Mater. Sci. Eng. C 2016 59 792 800 10.1016/j.msec.2015.10.087 26652434
    [Google Scholar]
  239. Chen Y. Liu Y.C. Sung Y.C. Ramjiawan R.R. Lin T.T. Chang C.C. Jeng K.S. Chang C.F. Liu C.H. Gao D.Y. Hsu F.F. Duyverman A.M. Kitahara S. Huang P. Dima S. Popescu I. Flaherty K.T. Zhu A.X. Bardeesy N. Jain R.K. Benes C.H. Duda D.G. Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors. Sci. Rep. 2017 7 1 44123 10.1038/srep44123 28276530
    [Google Scholar]
  240. Zhu D. Tao W. Zhang H. Liu G. Wang T. Zhang L. Zeng X. Mei L. Docetaxel (DTX)-loaded polydopamine-modified TPGS-PLA nanoparticles as a targeted drug delivery system for the treatment of liver cancer. Acta Biomater. 2016 30 144 154 10.1016/j.actbio.2015.11.031 26602819
    [Google Scholar]
  241. Liu H. Gao M. Xu H. Guan X. Lv L. Deng S. Zhang C. Tian Y. A promising emodin-loaded poly (lactic-co-glycolic acid)-d-a-tocopheryl polyethylene glycol 1000 succinate nanoparticles for liver cancer therapy. Pharm. Res. 2016 33 1 217 236 10.1007/s11095‑015‑1781‑4 26334502
    [Google Scholar]
  242. Wang J. Wang H. Li J. Liu Z. Xie H. Wei X. Lu D. Zhuang R. Xu X. Zheng S. iRGD-decorated polymeric nanoparticles for the efficient delivery of vandetanib to hepatocellular carcinoma: preparation and in vitro and in vivo evaluation. ACS Appl. Mater. Interfaces 2016 8 30 19228 19237 10.1021/acsami.6b03166 27381493
    [Google Scholar]
  243. Qin J. Yin P-H. Li Q. Sa Z-Q. Sheng X. Yang L. Huang T. Zhang M. Gao K-P. Chen Q-H. Ma J.W. Shen H.B. Anti-tumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma. Int. J. Nanomedicine 2012 7 369 379 10.2147/IJN.S27226 22334771
    [Google Scholar]
  244. Qin J. Yang L. Sheng X. Sa Z. Huang T. Li Q. Gao K. Chen Q. Ma J. Shen H. Antitumor effects of brucine immuno-nanoparticles on hepatocellular carcinoma in�vivo. Oncol. Lett. 2018 15 5 6137 6146 10.3892/ol.2018.8168 29731843
    [Google Scholar]
  245. Zheng N. Liu W. Li B. Nie H. Liu J. Cheng Y. Wang J. Dong H. Jia L. Co-delivery of sorafenib and metapristone encapsulated by CXCR4-targeted PLGA-PEG nanoparticles overcomes hepatocellular carcinoma resistance to sorafenib. J. Exp. Clin. Cancer Res. 2019 38 1 232 10.1186/s13046‑019‑1216‑x 31151472
    [Google Scholar]
  246. Wang H. Zhou L. Xie K. Wu J. Song P. Xie H. Zhou L. Liu J. Xu X. Shen Y. Zheng S. Polylactide-tethered prodrugs in polymeric nanoparticles as reliable nanomedicines for the efficient eradication of patient-derived hepatocellular carcinoma. Theranostics 2018 8 14 3949 3963 10.7150/thno.26161 30083272
    [Google Scholar]
  247. Zhang Y. Cui Z. Mei H. Xu J. Zhou T. Cheng F. Wang K. Angelica sinensis polysaccharide nanoparticles as a targeted drug delivery system for enhanced therapy of liver cancer. Carbohydr. Polym. 2019 219 143 154 10.1016/j.carbpol.2019.04.041 31151511
    [Google Scholar]
  248. Huang L. Chaurasiya B. Wu D. Wang H. Du Y. Tu J. Webster T.J. Sun C. Versatile redox-sensitive pullulan nanoparticles for enhanced liver targeting and efficient cancer therapy. Nanomedicine 2018 14 3 1005 1017 10.1016/j.nano.2018.01.015 29409820
    [Google Scholar]
  249. Rinaudo M. Chitin and chitosan: Properties and applications. Prog. Polym. Sci. 2006 31 7 603 632 10.1016/j.progpolymsci.2006.06.001
    [Google Scholar]
  250. Tang P. Sun Q. Yang H. Tang B. Pu H. Li H. Honokiol nanoparticles based on epigallocatechin gallate functionalized chitin to enhance therapeutic effects against liver cancer. Int. J. Pharm. 2018 545 1-2 74 83 10.1016/j.ijpharm.2018.04.060 29715531
    [Google Scholar]
  251. Kou C.H. Han J. Han X.L. Zhuang H.J. Zhao Z.M. Preparation and characterization of the Adriamycin‑loaded amphiphilic chitosan nanoparticles and their application in the treatment of liver cancer. Oncol. Lett. 2017 14 6 7833 7841 10.3892/ol.2017.7210 29344229
    [Google Scholar]
  252. Loutfy S.A. El-Din H.M.A. Elberry M.H. Allam N.G. Hasanin M. Abdellah A.M. Synthesis, characterization and cytotoxic evaluation of chitosan nanoparticles: in vitro liver cancer model. Adv. Nat. Sci.- Nanosci. Nanotechnol. 2016 7 3 035008 035006
    [Google Scholar]
  253. Cheng M. Zhu W. Li Q. Dai D. Hou Y. Anti-cancer efficacy of biotinylated chitosan nanoparticles in liver cancer. Oncotarget 2017 8 35 59068 59085 10.18632/oncotarget.19146 28938619
    [Google Scholar]
  254. Zhao X. Chen Q. Liu W. Li Y. Tang H. Liu X. Yang X. Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer. Int. J. Nanomedicine 2014 10 257 270 25565818
    [Google Scholar]
  255. Zhang J. Hu J. Chan H.F. Skibba M. Liang G. Chen M. iRGD decorated lipid-polymer hybrid nanoparticles for targeted co-delivery of doxorubicin and sorafenib to enhance anti-hepatocellular carcinoma efficacy. Nanomedicine 2016 12 5 1303 1311 10.1016/j.nano.2016.01.017 26964482
    [Google Scholar]
  256. Wu C-H. Lan C-H. Wu K-L. Wu Y.M. Jane W-N. Hsiao M. Wu H-C. Hepatocellular carcinoma-targeted nanoparticles for cancer therapy. Int. J. Oncol. 2018 52 2 389 401 29207071
    [Google Scholar]
  257. Zhao H. Wu M. Zhu L. Tian Y. Wu M. Li Y. Deng L. Jiang W. Shen W. Wang Z. Mei Z. Li P. Ran H. Zhou Z. Ren J. Cell-penetrating peptide-modified targeted drug-loaded phasetransformation lipid nanoparticles combined with low-intensity focused ultrasound for precision theranostics against hepatocellular carcinoma. Theranostics 2018 8 7 1892 1910 10.7150/thno.22386 29556363
    [Google Scholar]
  258. Namdari P. Negahdari B. Eatemadi A. Synthesis, properties and biomedical applications of carbon-based quantum dots: An updated review. Biomed. Pharmacother. 2017 87 209 222 10.1016/j.biopha.2016.12.108 28061404
    [Google Scholar]
  259. Mintz K.J. Zhou Y. Leblanc R.M. Recent development of carbon quantum dots regarding their optical properties, photoluminescence mechanism, and core structure. Nanoscale 2019 11 11 4634 4652 10.1039/C8NR10059D 30834912
    [Google Scholar]
  260. Mintz K.J. Guerrero B. Leblanc R.M. Photoinduced electron transfer in carbon dots with long-wavelength photoluminescence. J. Phys. Chem. C 2018 122 51 29507 29515 10.1021/acs.jpcc.8b06868
    [Google Scholar]
  261. Mintz K.J. Bartoli M. Rovere M. Zhou Y. Hettiarachchi S.D. Paudyal S. Chen J. Domena J.B. Liyanage P.Y. Sampson R. Khadka D. Pandey R.R. Huang S. Chusuei C.C. Tagliaferro A. Leblanc R.M. A deep investigation into the structure of carbon dots. Carbon 2021 173 433 447 10.1016/j.carbon.2020.11.017
    [Google Scholar]
  262. Song Y. Zhu S. Zhang S. Fu Y. Wang L. Zhao X. Yang B. Investigation from chemical structure to photoluminescent mechanism: a type of carbon dots from the pyrolysis of citric acid and an amine. J. Mater. Chem. C Mater. Opt. Electron. Devices 2015 3 23 5976 5984 10.1039/C5TC00813A
    [Google Scholar]
  263. Yan F. Jiang Y. Sun X. Bai Z. Zhang Y. Zhou X. Surface modification and chemical functionalization of carbon dots: a review. Mikrochim. Acta 2018 185 9 424 457 10.1007/s00604‑018‑2953‑9 30128831
    [Google Scholar]
  264. Gadzhimagomedova Z. Zolotukhin P. Kit O. Kirsanova D. Soldatov A. Nanocomposites for X-Ray photodynamic therapy. IJMS 2020 10.3390/ijms21114004
    [Google Scholar]
  265. Kirsanova D.Y. Gadzhimagomedova Z.M. Maksimov A.Y. Soldatov A.V. Nanomaterials for deep tumor treatment. Mini Rev. Med. Chem. 2021 21 6 677 688 10.2174/1389557520666201111161705 33176645
    [Google Scholar]
  266. Sebak A.A. El-Shenawy B.M. El-Safy S. El-Shazly M. From passive targeting to personalized nanomedicine: multidimensional insights on nanoparticles’ interaction with the tumor microenvironment. Curr. Pharm. Biotechnol. 2021 22 11 1444 1465 10.2174/1389201021666201211103856 33308126
    [Google Scholar]
  267. Wang Y. Wang Z. Xu C. Tian H. Chen X. A disassembling strategy overcomes the EPR effect and renal clearance dilemma of the multifunctional theranostic nanoparticles for cancer therapy. Biomaterials 2019 197 284 293 10.1016/j.biomaterials.2019.01.025 30677557
    [Google Scholar]
  268. Zhang L. Zhang M. Zhou L. Han Q. Chen X. Li S. Li L. Su Z. Wang C. Dual drug delivery and sequential release by amphiphilic Janus nanoparticles for liver cancer theranostics. Biomaterials 2018 181 113 125 10.1016/j.biomaterials.2018.07.060 30081302
    [Google Scholar]
  269. Miao L. Qi J. Zhao Q. Wu Q.N. Wei D.L. Wei X.L. Liu J. Chen J. Zeng Z.L. Ju H.Q. Luo H. Xu R.H. Targeting the STING pathway in tumor-associated macrophages regulates innate immune sensing of gastric cancer cells. Theranostics 2020 10 2 498 515 10.7150/thno.37745 31903134
    [Google Scholar]
  270. Weichand B. Popp R. Dziumbla S. Mora J. Strack E. Elwakeel E. Frank A.C. Scholich K. Pierre S. Syed S.N. Olesch C. Ringleb J. Ören B. Döring C. Savai R. Jung M. von Knethen A. Levkau B. Fleming I. Weigert A. Brüne B. S1PR1 on tumor-associated macrophages promotes lymphangiogenesis and metastasis via NLRP3/IL-1β. J. Exp. Med. 2017 214 9 2695 2713 10.1084/jem.20160392 28739604
    [Google Scholar]
  271. Petty A.J. Yang Y. Tumor-associated macrophages: implications in cancer immunotherapy. Immunotherapy 2017 9 3 289 302 10.2217/imt‑2016‑0135 28231720
    [Google Scholar]
  272. Ngambenjawong C. Gustafson H.H. Pun S.H. Progress in tumor-associated macrophage (TAM)-targeted therapeutics. Adv. Drug Deliv. Rev. 2017 114 206 221 10.1016/j.addr.2017.04.010 28449873
    [Google Scholar]
  273. Zhang K. Meng X. Yang Z. Dong H. Zhang X. Enhanced cancer therapy by hypoxia-responsive copper metal-organic frameworks nanosystem. Biomaterials 2020 258 120278 10.1016/j.biomaterials.2020.120278 32781328
    [Google Scholar]
  274. Xu W. Wang J. Li Q. Wu C. Wu L. Li K. Li Q. Han Q. Zhu J. Bai Y. Deng J. Lyu J. Wang Z. Cancer cell membrane-coated nanogels as a redox/pH dual-responsive drug carrier for tumor-targeted therapy. J. Mater. Chem. B Mater. Biol. Med. 2021 9 38 8031 8037 10.1039/D1TB00788B 34486010
    [Google Scholar]
  275. Ding Y. Sun Z. Tong Z. Zhang S. Min J. Xu Q. Zhou L. Mao Z. Xia H. Wang W. Tumor microenvironment-responsive multifunctional peptide coated ultrasmall gold nanoparticles and their application in cancer radiotherapy. Theranostics 2020 10 12 5195 5208 10.7150/thno.45017 32373207
    [Google Scholar]
  276. Yang Y. Yu Y. Chen H. Meng X. Ma W. Yu M. Li Z. Li C. Liu H. Zhang X. Xiao H. Yu Z. illuminating platinum transportation while maximizing therapeutic efcacy by gold nanoclusters via simultaneous near-infrared-i/ii imaging and glutathione scavenging. ACS Nano 2020 14 10 13536 13547 10.1021/acsnano.0c05541 32924505
    [Google Scholar]
  277. Yang Y. Liu X. Ma W. Xu Q. Chen G. Wang Y. Xiao H. Li N. Liang X.J. Yu M. Yu Z. Light-activatable liposomes for repetitive on-demand drug release and immunopotentiation in hypoxic tumor therapy. Biomaterials 2021 265 120456 10.1016/j.biomaterials.2020.120456 33099066
    [Google Scholar]
  278. Sun T. Han J. Liu S. Wang X. Wang Z.Y. Xie Z. Tailor-made semiconducting polymers for second near-infrared photothermal therapy of orthotopic liver cancer. ACS Nano 2019 13 6 7345 7354 10.1021/acsnano.9b03910 31188558
    [Google Scholar]
  279. Zhang Y. Wang X. Chu C. Zhou Z. Chen B. Pang X. Lin G. Lin H. Guo Y. Ren E. Lv P. Shi Y. Zheng Q. Yan X. Chen X. Liu G. Genetically engineered magnetic nanocages for cancer magneto-catalytic theranostics. Nat. Commun. 2020 11 1 5421 10.1038/s41467‑020‑19061‑9 33110072
    [Google Scholar]
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