Skip to content
2000
image of Lactoferrin-Conjugated Nanocarriers for Transformative Strategies in Cancer Management: New Insights on Breast Cancer Therapy

Abstract

Cancer represents a diverse and complex spectrum of diseases characterized by the abnormal growth and proliferation of cells, establishing a formidable global health challenge. Within the array of diverse cancers, breast cancer arises as one of the primary contributors to cancer-related fatalities in females. Breast cysts, thickenings, alterations in breast size or form, ., are all prevalent and well-known signs of breast cancer. Despite remarkable progression in cancer research and the abundance of potent drugs, the effectiveness of conventional therapy is still hindered by various complications. In this avenue, nanocarriers present considerable promise for delivering therapeutics to cancerous cells, however, still numerous challenges persist in achieving successful targeted drug delivery and localization. Recent progress has emphasized the utilization of ligand-functionalized nanocarriers to enhance the delivery at target tissues and improve uptake by cancer cells. This approach contributes to increased accuracy and efficacy, which ultimately leads to enhanced patient outcomes. Lactoferrin, a multifunctional glycoprotein, is currently receiving significant attention as a promising ligand for targeted drug delivery in cancerous cells, especially breast cancer cells. This review provides new insight into ligand-targeted therapy, emphasizing the key benefits and notable features of utilizing lactoferrin as a targeting ligand for delivering drug-loaded nanocarriers to tumor sites.

Loading

Article metrics loading...

/content/journals/cdd/10.2174/0115672018351146250307083901
2025-03-13
2025-05-04
Loading full text...

Full text loading...

References

  1. Padma V.V. An overview of targeted cancer therapy. Biomedicine 2015 5 4 19 10.7603/s40681‑015‑0019‑4 26613930
    [Google Scholar]
  2. Hassanpour S.H. Dehghani M. Review of cancer from perspective of molecular. J Cancer Res Pract. 2017 4 4 127 129 10.1016/j.jcrpr.2017.07.001
    [Google Scholar]
  3. Guan X. Cancer metastases: Challenges and opportunities. Acta Pharm. Sin. B 2015 5 5 402 418 10.1016/j.apsb.2015.07.005 26579471
    [Google Scholar]
  4. Pucci C. Martinelli C. Ciofani G. Innovative approaches for cancer treatment: Current perspectives and new challenges. Ecancermedicalscience 2019 13 961 10.3332/ecancer.2019.961 31537986
    [Google Scholar]
  5. Zugazagoitia J. Guedes C. Ponce S. Ferrer I. Molina-Pinelo S. Paz-Ares L. Current challenges in cancer treatment. Clin. Ther. 2016 38 7 1551 1566 10.1016/j.clinthera.2016.03.026 27158009
    [Google Scholar]
  6. Ferlay J. Soerjomataram I. Dikshit R. Eser S. Mathers C. Rebelo M. Parkin D.M. Forman D. Bray F. Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 2015 136 5 E359 E386 10.1002/ijc.29210 25220842
    [Google Scholar]
  7. 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]
  8. Wilkinson L. Gathani T. Understanding breast cancer as a global health concern. Br. J. Radiol. 2022 95 1130 20211033 10.1259/bjr.20211033 34905391
    [Google Scholar]
  9. Swaminathan H. Saravanamurali K. Yadav S.A. Extensive review on breast cancer its etiology, progression, prognostic markers, and treatment. Med. Oncol. 2023 40 8 238 10.1007/s12032‑023‑02111‑9 37442848
    [Google Scholar]
  10. Firatligil-Yildirir B. Yalcin-Ozuysal O. Nonappa N. Recent advances in lab-on-a-chip systems for breast cancer metastasis research. Nanoscale Adv. 2023 5 9 2375 2393 10.1039/D2NA00823H 37143816
    [Google Scholar]
  11. Winters S. Martin C. Murphy D. Shokar N.K. Lakshmanaswamy R. Breast cancer epidemiology, prevention, and screening. Progress in Molecular Biology and Translational Science. Elsevier, Academic Press 2017 1 32 10.1016/bs.pmbts.2017.07.002
    [Google Scholar]
  12. Barba D. León-Sosa A. Lugo P. Suquillo D. Torres F. Surre F. Trojman L. Caicedo A. Breast cancer, screening and diagnostic tools: All you need to know. Crit. Rev. Oncol. Hematol. 2021 157 103174 10.1016/j.critrevonc.2020.103174 33249359
    [Google Scholar]
  13. Feng Y. Spezia M. Huang S. Yuan C. Zeng Z. Zhang L. Ji X. Liu W. Huang B. Luo W. Liu B. Lei Y. Du S. Vuppalapati A. Luu H.H. Haydon R.C. He T.C. Ren G. Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis. 2018 5 2 77 106 10.1016/j.gendis.2018.05.001 30258937
    [Google Scholar]
  14. Jain V. Kumar H. Anod H.V. Chand P. Gupta N.V. Dey S. Kesharwani S.S. A review of nanotechnology-based approaches for breast cancer and triple-negative breast cancer. J. Control. Release 2020 326 628 647 10.1016/j.jconrel.2020.07.003 32653502
    [Google Scholar]
  15. Russo J. Rezai M. Kocdor M.A. Canturk N.Z. Molecular classification of breast cancer. Breast Cancer Essentials. Springer Cham 2021 33 38 10.1007/978‑3‑030‑73147‑2_4
    [Google Scholar]
  16. Alhmoud J.F. Woolley J.F. Al Moustafa A.E. Malki M.I. DNA damage/repair management in cancers. Cancers 2020 12 4 1050 10.3390/cancers12041050 32340362
    [Google Scholar]
  17. Akram M. Iqbal M. Daniyal M. Khan A.U. Awareness and current knowledge of breast cancer. Biol. Res. 2017 50 1 33 10.1186/s40659‑017‑0140‑9 28969709
    [Google Scholar]
  18. Saini S. Gulati N. Awasthi R. Arora V. Singh S.K. Kumar S. Gupta G. Dua K. Pahwa R. Dureja H. Monoclonal antibodies and antibody-drug conjugates as emerging therapeutics for breast cancer treatment. Curr. Drug Deliv. 2024 21 7 993 1009 10.2174/1567201820666230731094258 37519200
    [Google Scholar]
  19. Smolarz B. Nowak A.Z. Romanowicz H. Breast cancer-epidemiology, classification, pathogenesis and treatment (Review of literature). Cancers 2022 14 10 2569 10.3390/cancers14102569 35626173
    [Google Scholar]
  20. Kamińska M. Ciszewski T. Łopacka-Szatan K. Miotła P. Starosławska E. Breast cancer risk factors. Prz. Menopauzalny. 2015 14 3 196 202 10.5114/pm.2015.54346 26528110
    [Google Scholar]
  21. Kontomanolis E.N. Koutras A. Syllaios A. Schizas D. Mastoraki A. Garmpis N. Diakosavvas M. Angelou K. Tsatsaris G. Pagkalos A. Ntounis T. Fasoulakis Z. Role of oncogenes and tumor-suppressor genes in carcinogenesis: A review. Anticancer Res. 2020 40 11 6009 6015 10.21873/anticanres.14622 33109539
    [Google Scholar]
  22. Pistritto G. Trisciuoglio D. Ceci C. Garufi A. D’Orazi G. Apoptosis as anticancer mechanism: Function and dysfunction of its modulators and targeted therapeutic strategies. Aging 2016 8 4 603 619 10.18632/aging.100934 27019364
    [Google Scholar]
  23. Watkins E.J. Overview of breast cancer. JAAPA 2019 32 10 13 17 10.1097/01.JAA.0000580524.95733.3d 31513033
    [Google Scholar]
  24. Nounou M.I. ElAmrawy F. Ahmed N. Abdelraouf K. Goda S. Syed-Sha-Qhattal H. Breast cancer: Conventional diagnosis and treatment modalities and recent patents and technologies supplementary issue: Targeted therapies in breast cancer treatment. Breast Cancer 2015 9 Suppl. 2 BCBCR.S29420 10.4137/BCBCR.S29420 26462242
    [Google Scholar]
  25. Harbeck N. Gnant M. Breast cancer. Lancet 2017 389 10074 1134 1150 10.1016/S0140‑6736(16)31891‑8 27865536
    [Google Scholar]
  26. Barzaman K. Karami J. Zarei Z. Hosseinzadeh A. Kazemi M.H. Moradi-Kalbolandi S. Safari E. Farahmand L. Breast cancer: Biology, biomarkers, and treatments. Int. Immunopharmacol. 2020 84 106535 10.1016/j.intimp.2020.106535 32361569
    [Google Scholar]
  27. García-Aranda M. Redondo M. Immunotherapy: A challenge of breast cancer treatment. Cancers 2019 11 12 1822 10.3390/cancers11121822 31756919
    [Google Scholar]
  28. Tokumaru Y. Joyce D. Takabe K. Current status and limitations of immunotherapy for breast cancer. Surgery 2020 167 3 628 630 10.1016/j.surg.2019.09.018 31623855
    [Google Scholar]
  29. Alshareeda A.T. Nur Khatijah M.Z. Al-Sowayan B.S. Nanotechnology: A revolutionary approach to prevent breast cancer recurrence. Asian J. Surg. 2023 46 1 13 17 10.1016/j.asjsur.2022.03.002 35361551
    [Google Scholar]
  30. Ahmad A. Breast cancer statistics: Recent trends. Adv. Exp. Med. Biol. 2019 1152 1 7 10.1007/978‑3‑030‑20301‑6_1 31456176
    [Google Scholar]
  31. Das M. Mohanty C. Sahoo S.K. Ligand-based targeted therapy for cancer tissue. Expert Opin. Drug Deliv. 2009 6 3 285 304 10.1517/17425240902780166 19327045
    [Google Scholar]
  32. Chaurasia M. Singh R. Sur S. Flora S.J.S. A review of FDA approved drugs and their formulations for the treatment of breast cancer. Front. Pharmacol. 2023 14 1184472 10.3389/fphar.2023.1184472 37576816
    [Google Scholar]
  33. Tran P. Lee S.E. Kim D.H. Pyo Y.C. Park J.S. Recent advances of nanotechnology for the delivery of anticancer drugs for breast cancer treatment. J. Pharm. Investig. 2020 50 3 261 270 10.1007/s40005‑019‑00459‑7
    [Google Scholar]
  34. Afzal M. Nanomedicine in treatment of breast cancer – A challenge to conventional therapy. Semin. Cancer Biol. 2021 69 279 292 10.1016/j.semcancer.2019.12.016 31870940
    [Google Scholar]
  35. Tang X. Loc W.S. Dong C. Matters G.L. Butler P.J. Kester M. Meyers C. Jiang Y. Adair J.H. The use of nanoparticulates to treat breast cancer. Nanomedicine 2017 12 19 2367 2388 10.2217/nnm‑2017‑0202 28868970
    [Google Scholar]
  36. Bertrand N. Wu J. Xu X. Kamaly N. Farokhzad O.C. Cancer nanotechnology: The impact of passive and active targeting in the era of modern cancer biology. Adv. Drug Deliv. Rev. 2014 66 2 25 10.1016/j.addr.2013.11.009 24270007
    [Google Scholar]
  37. Mi P. Cabral H. Kataoka K. Ligand-installed nanocarriers toward precision therapy. Adv. Mater. 2020 32 13 1902604 10.1002/adma.201902604 31353770
    [Google Scholar]
  38. Yoo J. Park C. Yi G. Lee D. Koo H. Active targeting strategies using biological ligands for nanoparticle drug delivery systems. Cancers 2019 11 5 640 10.3390/cancers11050640 31072061
    [Google Scholar]
  39. Bandyopadhyay A. Das T. Nandy S. Sahib S. Preetam S. Gopalakrishnan A.V. Dey A. Ligand-based active targeting strategies for cancer theranostics. Naunyn Schmiedebergs Arch. Pharmacol. 2023 396 12 3417 3441 10.1007/s00210‑023‑02612‑4 37466702
    [Google Scholar]
  40. Kumari P. Ghosh B. Biswas S. Nanocarriers for cancer-targeted drug delivery. J. Drug Target. 2016 24 3 179 191 10.3109/1061186X.2015.1051049 26061298
    [Google Scholar]
  41. Onzi G. Guterres S.S. Pohlmann A.R. Frank L.A. Active targeting of nanocarriers The ADME Encyclopedia Springer Cham 2021 1 13 10.1007/978‑3‑030‑51519‑5_109‑1
    [Google Scholar]
  42. Srinivasarao M. Low P.S. Ligand-targeted drug delivery. Chem. Rev. 2017 117 19 12133 12164 10.1021/acs.chemrev.7b00013 28898067
    [Google Scholar]
  43. Zhuang C. Guan X. Ma H. Cong H. Zhang W. Miao Z. Small molecule-drug conjugates: A novel strategy for cancer-targeted treatment. Eur. J. Med. Chem. 2019 163 883 895 10.1016/j.ejmech.2018.12.035 30580240
    [Google Scholar]
  44. Gonzalez-Rodriguez D. Barakat A.I. Dynamics of receptor-mediated nanoparticle internalization into endothelial cells. PLoS One 2015 10 4 e0122097 10.1371/journal.pone.0122097 25901833
    [Google Scholar]
  45. Karra N. Benita S. The ligand nanoparticle conjugation approach for targeted cancer therapy. Curr. Drug Metab. 2012 13 1 22 41 10.2174/138920012798356899 21892918
    [Google Scholar]
  46. Elzoghby A.O. Abdelmoneem M.A. Hassanin I.A. Abd Elwakil M.M. Elnaggar M.A. Mokhtar S. Fang J.Y. Elkhodairy K.A. Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand. Biomaterials 2020 263 120355 10.1016/j.biomaterials.2020.120355 32932142
    [Google Scholar]
  47. Adlerova L. Bartoskova A. Faldyna M. Lactoferrin: A review. Vet. Med. 2008 53 9 457 468 10.17221/1978‑VETMED
    [Google Scholar]
  48. Kanwar J. Roy K. Patel Y. Zhou S.F. Singh M. Singh D. Nasir M. Sehgal R. Sehgal A. Singh R. Garg S. Kanwar R. Multifunctional iron bound lactoferrin and nanomedicinal approaches to enhance its bioactive functions. Molecules 2015 20 6 9703 9731 10.3390/molecules20069703 26016555
    [Google Scholar]
  49. Kanwar J.R. Mahidhara G. Roy K. Sasidharan S. Krishnakumar S. Prasad N. Sehgal R. Kanwar R.K. Fe-bLf nanoformulation targets survivin to kill colon cancer stem cells and maintains absorption of iron, calcium and zinc. Nanomedicine 2015 10 1 35 55 10.2217/nnm.14.132 25017148
    [Google Scholar]
  50. Mohamad R.H. Zekry Z.K. Al-Mehdar H.A. Salama O. El-Shaieb S.E. El-Basmy A.A. Al-said M.G.A.M. Sharawy S.M. Camel milk as an adjuvant therapy for the treatment of type 1 diabetes: Verification of a traditional ethnomedical practice. J. Med. Food 2009 12 2 461 465 10.1089/jmf.2008.0009 19459752
    [Google Scholar]
  51. Takayama Y. Aoki R. Uchida R. Tajima A. Aoki-Yoshida A. Role of CXC chemokine receptor type 4 as a lactoferrin receptor. Biochem. Cell Biol. 2017 95 1 57 63 10.1139/bcb‑2016‑0039 28075616
    [Google Scholar]
  52. Grey A. Banovic T. Zhu Q. Watson M. Callon K. Palmano K. Ross J. Naot D. Reid I.R. Cornish J. The low-density lipoprotein receptor-related protein 1 is a mitogenic receptor for lactoferrin in osteoblastic cells. Mol. Endocrinol. 2004 18 9 2268 2278 10.1210/me.2003‑0456 15178744
    [Google Scholar]
  53. Ando K. Hasegawa K. Shindo K. Furusawa T. Fujino T. Kikugawa K. Nakano H. Takeuchi O. Akira S. Akiyama T. Gohda J. Inoue J. Hayakawa M. Human lactoferrin activates NF‐κB through the Toll‐like receptor 4 pathway while it interferes with the lipopolysaccharide‐stimulated TLR4 signaling. FEBS J. 2010 277 9 2051 2066 10.1111/j.1742‑4658.2010.07620.x 20345905
    [Google Scholar]
  54. Lesná J. Tichá A. Hyšpler R. Musil F. Bláha V. Sobotka L. Zadák Z. Šmahelová A. Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: Impact of weight reduction. Nutr. Diabetes 2015 5 11 e183 10.1038/nutd.2015.33 26524638
    [Google Scholar]
  55. Spuch C. Ortolano S. Navarro C. LRP-1 and LRP-2 receptors function in the membrane neuron. Trafficking mechanisms and proteolytic processing in Alzheimer’s disease. Front. Physiol. 2012 3 3 269 10.3389/fphys.2012.00269 22934024
    [Google Scholar]
  56. Akiyama Y. Oshima K. Kuhara T. Shin K. Abe F. Iwatsuki K. Nadano D. Matsuda T. A lactoferrin-receptor, intelectin 1, affects uptake, sub-cellular localization and release of immunochemically detectable lactoferrin by intestinal epithelial Caco-2 cells. J. Biochem. 2013 154 5 437 448 10.1093/jb/mvt073 23921499
    [Google Scholar]
  57. Kell D.B. Heyden E.L. Pretorius E. The biology of lactoferrin, an iron-binding protein that can help defend against viruses and bacteria. Front. Immunol. 2020 11 1221 10.3389/fimmu.2020.01221 32574271
    [Google Scholar]
  58. Superti F. Lactoferrin from bovine milk: A protective companion for life. Nutrients 2020 12 9 2562 10.3390/nu12092562 32847014
    [Google Scholar]
  59. Sabra S. Agwa M.M. Lactoferrin, a unique molecule with diverse therapeutical and nanotechnological applications. Int. J. Biol. Macromol. 2020 164 1046 1060 10.1016/j.ijbiomac.2020.07.167 32707283
    [Google Scholar]
  60. Wang B. Timilsena Y.P. Blanch E. Adhikari B. Lactoferrin: Structure, function, denaturation and digestion. Crit. Rev. Food Sci. Nutr. 2019 59 4 580 596 10.1080/10408398.2017.1381583 28933602
    [Google Scholar]
  61. Gupta P. Perrine C. Mei Z. Scanlon K. Iron, anemia, and iron deficiency anemia among young children in the United States. Nutrients 2016 8 6 330 10.3390/nu8060330 27249004
    [Google Scholar]
  62. Cao X. Ren Y. Lu Q. Wang K. Wu Y. Wang Y. Zhang Y. Cui X. Yang Z. Chen Z. Lactoferrin: A glycoprotein that plays an active role in human health. Front. Nutr. 2023 9 1018336 10.3389/fnut.2022.1018336 36712548
    [Google Scholar]
  63. Kruzel M.L. Harari Y. Mailman D. Actor J.K. Zimecki M. Differential effects of prophylactic, concurrent and therapeutic lactoferrin treatment on LPS-induced inflammatory responses in mice. Clin. Exp. Immunol. 2002 130 1 25 31 10.1046/j.1365‑2249.2002.01956.x 12296849
    [Google Scholar]
  64. García-Montoya I.A. Cendón T.S. Arévalo-Gallegos S. Rascón-Cruz Q. Lactoferrin a multiple bioactive protein: An overview. Biochim. Biophys. Acta, Gen. Subj. 2012 1820 3 226 236 10.1016/j.bbagen.2011.06.018 21726601
    [Google Scholar]
  65. Rascón-Cruz Q. Espinoza-Sánchez E.A. Siqueiros-Cendón T.S. Nakamura-Bencomo S.I. Arévalo-Gallegos S. Iglesias-Figueroa B.F. Lactoferrin: A glycoprotein involved in immunomodulation, anticancer, and antimicrobial processes. Molecules 2021 26 1 205 10.3390/molecules26010205 33401580
    [Google Scholar]
  66. Vogel H.J. Lactoferrin, a bird’s eye view. Biochem. Cell Biol. 2012 90 3 233 244 10.1139/o2012‑016 22540735
    [Google Scholar]
  67. Hao L. Shan Q. Wei J. Ma F. Sun P. Lactoferrin: Major physiological functions and applications. Curr. Protein Pept. Sci. 2019 20 2 139 144 10.2174/1389203719666180514150921 29756573
    [Google Scholar]
  68. Ahmed K. Saikat A. Moni A. Kakon S. Islam M. Uddin M. Lactoferrin: Potential functions, pharmacological insights, and therapeutic promises. JABET 2021 4 2 223 237 10.5455/jabet.2021.d123
    [Google Scholar]
  69. Bukowska-Ośko I. Sulejczak D. Kaczyńska K. Kleczkowska P. Kramkowski K. Popiel M. Wietrak E. Kowalczyk P. Lactoferrin as a human genome “Guardian”—An overall point of view. Int. J. Mol. Sci. 2022 23 9 5248 10.3390/ijms23095248 35563638
    [Google Scholar]
  70. Godínez-Chaparro B. Guzmán-Mejía F. Drago-Serrano M.E. Lactoferrin and its potential impact for the relief of pain: A preclinical approach. Pharmaceuticals 2021 14 9 868 10.3390/ph14090868 34577568
    [Google Scholar]
  71. Sienkiewicz M. Jaśkiewicz A. Tarasiuk A. Fichna J. Lactoferrin: an overview of its main functions, immunomodulatory and antimicrobial role, and clinical significance. Crit. Rev. Food Sci. Nutr. 2022 62 22 6016 6033 10.1080/10408398.2021.1895063 33685299
    [Google Scholar]
  72. Ul A. Wani H. Angad D.G. Veterinary, Lactoferrin a potential therapeutic candidate. Sci. World 2021 1 4 105 111
    [Google Scholar]
  73. Giansanti F. Panella G. Leboffe L. Antonini G. Lactoferrin from milk: Nutraceutical and pharmacological properties. Pharmaceuticals 2016 9 4 61 10.3390/ph9040061 27690059
    [Google Scholar]
  74. Baker H.M. Baker E.N. A structural perspective on lactoferrin function Biochem. Cell Biol. 2012 90 3 320 328 10.1139/o11‑071 22292559
    [Google Scholar]
  75. Actor J.K. Hwang S.A. Kruzel M.L. Lactoferrin as a Natural Immune Modulator. Curr. Pharm. Des. 2009 15 17 1956 1973 10.2174/138161209788453202 19519436
    [Google Scholar]
  76. Tran T.H. Tran P.T.T. Truong D.H. Lactoferrin and nanotechnology: The potential for cancer treatment. Pharmaceutics 2023 15 5 1362 10.3390/pharmaceutics15051362 37242604
    [Google Scholar]
  77. Carbone D.P. Gandara D.R. Antonia S.J. Zielinski C. Paz-Ares L. Non–small-cell lung cancer: Role of the immune system and potential for immunotherapy. J. Thorac. Oncol. 2015 10 7 974 984 10.1097/JTO.0000000000000551 26134219
    [Google Scholar]
  78. Lin J.J. Cancer treatment. Caring for Patients Across the Cancer Care Continuum ; Nekhlyudov, L., Goel, M., Lin, J., Overholser, L., Peairs, K. Eds.; Springer Cham 2019 93 123 10.1007/978‑3‑030‑01896‑2_5 1650686
    [Google Scholar]
  79. Xiao B. Ma L. Merlin D. Nanoparticle-mediated co-delivery of chemotherapeutic agent and SiRNA for combination cancer therapy. Expert Opin Drug Deliv. 2018 14 1 65 73 10.1080/17425247.2016.1205583 27337289
    [Google Scholar]
  80. Chen W.H. Lecaros R.L.G. Tseng Y.C. Huang L. Hsu Y.C. Nanoparticle delivery of HIF1α siRNA combined with photodynamic therapy as a potential treatment strategy for head-and-neck cancer. Cancer Lett. 2015 359 1 65 74 10.1016/j.canlet.2014.12.052 25596376
    [Google Scholar]
  81. Pan S. Weng H. Hu G. Wang S. Zhao T. Yao X. Liao L. Zhu X. Ge Y. Lactoferrin may inhibit the development of cancer via its immunostimulatory and immunomodulatory activities. Int. J. Oncol. 2021 59 5 85 10.3892/ijo.2021.5265
    [Google Scholar]
  82. Woźniak M. Pastuch-Gawołek G. Makuch S. Wiśniewski J. Ziółkowski P. Szeja W. Krawczyk M. Agrawal S. Overcoming hypoxia-induced chemoresistance in cancer using a novel Glycoconjugate of Methotrexate. Pharmaceuticals 2020 14 1 13 10.3390/ph14010013 33374474
    [Google Scholar]
  83. Bui B.P. Nguyen P.L. Lee K. Cho J. Hypoxia-inducible factor-1: A novel therapeutic target for the management of cancer, drug resistance, and cancer-related pain. Cancers 2022 14 24 6054 10.3390/cancers14246054 36551540
    [Google Scholar]
  84. Foglizzo V. Marchiò S. Nanoparticles as physically- And biochemically-tuned drug formulations for cancers therapy. Cancers 2022 14 10 2473 10.3390/cancers14102473 35626078
    [Google Scholar]
  85. Zhang Z. Yang J. Min Q. Ling C. Maiti D. Xu J. Qin L. Yang K. Holo‐Lactoferrin modified liposome for relieving tumor hypoxia and enhancing radiochemotherapy of cancer. Small 2019 15 6 1803703 10.1002/smll.201803703 30645056
    [Google Scholar]
  86. Zhao C. Zhu X. Tan J. Mei C. Cai X. Kong F. Lipid-based nanoparticles to address the limitations of GBM therapy by overcoming the blood-brain barrier, targeting glioblastoma stem cells, and counteracting the immunosuppressive tumor microenvironment. Biomed. Pharmacother. 2024 171 171 116113 10.1016/j.biopha.2023.116113 38181717
    [Google Scholar]
  87. Xue Y. Gao Y. Meng F. Luo L. Recent progress of nanotechnology-based theranostic systems in cancer treatments. Cancer Biol. Med. 2021 18 2 336 351 10.20892/j.issn.2095‑3941.2020.0510 33861527
    [Google Scholar]
  88. Zu M. Ma Y. Cannup B. Xie D. Jung Y. Zhang J. Yang C. Gao F. Merlin D. Xiao B. Oral delivery of natural active small molecules by polymeric nanoparticles for the treatment of inflammatory bowel diseases. Adv. Drug Deliv. Rev. 2021 176 113887 10.1016/j.addr.2021.113887 34314785
    [Google Scholar]
  89. Shilpi S. Vimal V.D. Soni V. Assessment of lactoferrin-conjugated solid lipid nanoparticles for efficient targeting to the lung. Prog. Biomater. 2015 4 1 55 63 10.1007/s40204‑015‑0037‑z 29470795
    [Google Scholar]
  90. Boopathi E. Den R.B. Thangavel C. Innate immune system in the context of radiation therapy for cancer. Cancers 2023 15 15 3972 10.3390/cancers15153972 37568788
    [Google Scholar]
  91. Busato F. Khouzai B.E. Mognato M. Biological mechanisms to reduce radioresistance and increase the efficacy of radiotherapy: State of the art. Int. J. Mol. Sci. 2022 23 18 10211 10.3390/ijms231810211 36142122
    [Google Scholar]
  92. Su X.Y. Liu P.D. Wu H. Gu N. Enhancement of radiosensitization by metal-based nanoparticles in cancer radiation therapy. Cancer Biol. Med. 2014 11 2 86 91 10.7497/j.issn.2095‑3941.2014.02.003 25009750
    [Google Scholar]
  93. Cutone A. Rosa L. Ianiro G. Lepanto M.S. Bonaccorsi di Patti M.C. Valenti P. Musci G. Lactoferrin’s anti-cancer properties: Safety, selectivity, and wide range of action. Biomolecules 2020 10 3 456 10.3390/biom10030456 32183434
    [Google Scholar]
  94. Agwa M.M. Sabra S. Lactoferrin coated or conjugated nanomaterials as an active targeting approach in nanomedicine. Int. J. Biol. Macromol. 2021 167 1527 1543 10.1016/j.ijbiomac.2020.11.107 33212102
    [Google Scholar]
  95. Elfinger M. Maucksch C. Rudolph C. Characterization of lactoferrin as a targeting ligand for nonviral gene delivery to airway epithelial cells. Biomaterials 2007 28 23 3448 3455 10.1016/j.biomaterials.2007.04.011 17475321
    [Google Scholar]
  96. Abdelmoneem M.A. Abd Elwakil M.M. Khattab S.N. Helmy M.W. Bekhit A.A. Abdulkader M.A. Zaky A. Teleb M. Elkhodairy K.A. Albericio F. Elzoghby A.O. Lactoferrin-dual drug nanoconjugate: Synergistic anti-tumor efficacy of docetaxel and the NF-κB inhibitor celastrol. Mater. Sci. Eng. C 2021 118 111422 10.1016/j.msec.2020.111422 33255023
    [Google Scholar]
  97. Kondapi A.K. Targeting cancer with lactoferrin nanoparticles: Recent advances. Nanomedicine 2020 15 21 2071 2083 10.2217/nnm‑2020‑0090 32779524
    [Google Scholar]
  98. Zhang Y. Lima C.F. Rodrigues L.R. Anticancer effects of lactoferrin: Underlying mechanisms and future trends in cancer therapy. Nutr. Rev. 2014 72 12 763 773 10.1111/nure.12155 25406879
    [Google Scholar]
  99. Pang Z. Feng L. Hua R. Chen J. Gao H. Pan S. Jiang X. Zhang P. Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats. Mol. Pharm. 2010 7 6 1995 2005 10.1021/mp100277h 20957995
    [Google Scholar]
  100. Etman S.M. Abdallah O.Y. Mehanna R.A. Elnaggar Y.S.R. Lactoferrin/Hyaluronic acid double-coated lignosulfonate nanoparticles of quinacrine as a controlled release biodegradable nanomedicine targeting pancreatic cancer. Int. J. Pharm. 2020 578 119097 10.1016/j.ijpharm.2020.119097 32032904
    [Google Scholar]
  101. Massodi I. Thomas E. Raucher D. Application of thermally responsive elastin-like polypeptide fused to a lactoferrin-derived peptide for treatment of pancreatic cancer. Molecules 2009 14 6 1999 2015 10.3390/molecules14061999 19513001
    [Google Scholar]
  102. Abdelaziz H.M. Elzoghby A.O. Helmy M.W. Abdelfattah E.Z.A. Fang J.Y. Samaha M.W. Freag M.S. Inhalable lactoferrin/chondroitin-functionalized monoolein nanocomposites for localized lung cancer targeting. ACS Biomater. Sci. Eng. 2020 6 2 1030 1042 10.1021/acsbiomaterials.9b01639 33464839
    [Google Scholar]
  103. Kabary D.M. Helmy M.W. Elkhodairy K.A. Fang J.Y. Elzoghby A.O. Hyaluronate/lactoferrin layer-by-layer-coated lipid nanocarriers for targeted co-delivery of rapamycin and berberine to lung carcinoma. Colloids Surf. B Biointerfaces 2018 169 183 194 10.1016/j.colsurfb.2018.05.008 29775813
    [Google Scholar]
  104. Balak N.K.J. Kurmi D. Gajbhiye V. Kayat J. Lactoferrin-conjugated dendritic nanoconstructs for lung targeting of methotrexate. J. Pharm. Sci. 2012 101 2271 2280 10.1002/jps
    [Google Scholar]
  105. Pandey V. Gajbhiye K.R. Soni V. Lactoferrin-appended solid lipid nanoparticles of paclitaxel for effective management of bronchogenic carcinoma. Drug Deliv. 2015 22 2 199 205 10.3109/10717544.2013.877100 24467582
    [Google Scholar]
  106. Attri K. Chudasama B. Mahajan R.L. Choudhury D. Therapeutic potential of lactoferrin-coated iron oxide nanospheres for targeted hyperthermia in gastric cancer. Sci. Rep. 2023 13 1 17875 10.1038/s41598‑023‑43725‑3 37857677
    [Google Scholar]
  107. Li H. Tong Y. Bai L. Ye L. Zhong L. Duan X. Zhu Y. Lactoferrin functionalized PEG-PLGA nanoparticles of shikonin for brain targeting therapy of glioma. Int. J. Biol. Macromol. 2018 107 Pt A 204 211 10.1016/j.ijbiomac.2017.08.155 28863897
    [Google Scholar]
  108. Fang J.H. Chiu T.L. Huang W.C. Lai Y.H. Hu S.H. Chen Y.Y. Chen S.Y. Dual-targeting lactoferrin-conjugated polymerized magnetic polydiacetylene-assembled nanocarriers with self-responsive fluorescence/magnetic resonance imaging for in vivo brain tumor therapy. Adv. Healthc. Mater. 2016 5 6 688 695 10.1002/adhm.201500750 26820074
    [Google Scholar]
  109. Zhang J. Xiao X. Zhu J. Gao Z. Lai X. Zhu X. Mao G. Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy. Int. J. Nanomedicine 2018 13 3039 3051 10.2147/IJN.S161163 29861635
    [Google Scholar]
  110. Kumari S. Kondapi A.K. Lactoferrin nanoparticle mediated targeted delivery of 5-fluorouracil for enhanced therapeutic efficacy. Int. J. Biol. Macromol. 2017 95 232 237 10.1016/j.ijbiomac.2016.10.110 27864056
    [Google Scholar]
  111. Almowalad J. Laskar P. Somani S. Meewan J. Tate R.J. Dufès C. Lactoferrin-and dendrimer-bearing gold nanocages for stimulus-free DNA delivery to prostate cancer cells. Int. J. Nanomedicine 2022 17 1409 1421 10.2147/IJN.S347574 35369035
    [Google Scholar]
  112. Muj C. Mukhopadhyay S. Jana P. Kondapi A.K. Synergistic action of lactoferrin in enhancing the safety and effectiveness of docetaxel treatment against prostate cancer. Cancer Chemother. Pharmacol. 2023 91 5 375 387 10.1007/s00280‑023‑04524‑9 36977771
    [Google Scholar]
  113. Altwaijry N. Somani S. Parkinson J.A. Tate R.J. Keating P. Warzecha M. Mackenzie G.R. Leung H.Y. Dufès C. Regression of prostate tumors after intravenous administration of lactoferrin-bearing polypropylenimine dendriplexes encoding TNF-α, TRAIL, and interleukin-12. Drug Deliv. 2018 25 1 679 689 10.1080/10717544.2018.1440666 29493296
    [Google Scholar]
  114. Roy K. Kanwar R.K. Kanwar J.R. LNA aptamer based multi-modal, Fe 3 O 4 -saturated lactoferrin (Fe 3 O 4 -bLf) nanocarriers for triple positive (EpCAM, CD133, CD44) colon tumor targeting and NIR, MRI and CT imaging. Biomaterials 2015 71 84 99 10.1016/j.biomaterials.2015.07.055 26318819
    [Google Scholar]
  115. Bovine Lactoferrin supplement in improving taste in patients with cancer receiving chemotherapy. clinicaltrials.gov NCT01941810, 2018
  116. Bovine Lactoferrin in reducing taste disturbances in patients with colorectal cancer receiving oxaliplatin-based chemotherapy. clinicaltrials.gov NCT01596634, 2018
  117. Safety/​efficacy study of oral recombinant human lactoferrin in renal cell carcinoma. clinicaltrials.gov NCT00095186, 2008
  118. Safety and efficacy of talactoferrin in previously treated patients with non-small cell lung cancer (FORTIS-M). Patent NCT00707304, 2012
  119. Metallic taste before, during and after treatment of head and neck cancer (TORCAD). clinicaltrials.gov NCT03558789, 2023
  120. Halder A. Jethwa M. Mukherjee P. Ghosh S. Das S. Helal Uddin A.B.M. Mukherjee A. Chatterji U. Roy P. Lactoferrin-tethered betulinic acid nanoparticles promote rapid delivery and cell death in triple negative breast and laryngeal cancer cells. Artif. Cells Nanomed. Biotechnol. 2020 48 1 1362 1371 10.1080/21691401.2020.1850465 33284038
    [Google Scholar]
  121. Sabra S.A. Sheweita S.A. Haroun M. Ragab D. Eldemellawy M.A. Xia Y. Goodale D. Allan A.L. Elzoghby A.O. Rohani S. Magnetically Guided self-assembled protein micelles for enhanced delivery of dasatinib to human triple-negative breast cancer cells. J. Pharm. Sci. 2019 108 5 1713 1725 10.1016/j.xphs.2018.11.044 30528944
    [Google Scholar]
  122. Mokhtar S. Khattab S.N. Elkhodairy K.A. Teleb M. Bekhit A.A. Elzoghby A.O. Sallam M.A. Methotrexate-lactoferrin targeted exemestane cubosomes for synergistic breast cancer therapy. Front Chem. 2022 10 847573 10.3389/fchem.2022.847573 35392419
    [Google Scholar]
  123. Metawea O.R.M. Abdelmoneem M.A. Haiba N.S. Khalil H.H. Teleb M. Elzoghby A.O. Khafaga A.F. Noreldin A.E. Albericio F. Khattab S.N. A novel ‘smart’ PNIPAM-based copolymer for breast cancer targeted therapy: Synthesis, and characterization of dual pH/temperature-responsive lactoferrin-targeted PNIPAM-co-AA. Colloids Surf. B Biointerfaces 2021 202 111694 10.1016/j.colsurfb.2021.111694 33740633
    [Google Scholar]
  124. Ning S. Zheng Y. Qiao K. Li G. Bai Q. Xu S. Laser-triggered combination therapy by iron sulfide-doxorubicin@functionalized nanozymes for breast cancer therapy. J. Nanobiotechnology 2021 19 1 344 10.1186/s12951‑021‑01023‑y 34706736
    [Google Scholar]
  125. El-Lakany S.A. Elgindy N.A. Helmy M.W. Abu-Serie M.M. Elzoghby A.O. Lactoferrin-decorated vs PEGylated zein nanospheres for combined aromatase inhibitor and herbal therapy of breast cancer. Expert Opin. Drug Deliv. 2018 15 9 835 850 10.1080/17425247.2018.1505858 30067113
    [Google Scholar]
  126. Ali O.M. Bekhit A.A. Khattab S.N. Helmy M.W. Abdel-Ghany Y.S. Teleb M. Elzoghby A.O. Synthesis of lactoferrin mesoporous silica nanoparticles for pemetrexed/ellagic acid synergistic breast cancer therapy. Colloids Surf. B Biointerfaces 2020 188 110824 10.1016/j.colsurfb.2020.110824 32023511
    [Google Scholar]
  127. Salah M. Sallam M.A. Abdelmoneem M.A. Teleb M. Elkhodairy K.A. Bekhit A.A. Khafaga A.F. Noreldin A.E. Elzoghby A.O. Khattab S.N. Sequential delivery of novel triple drug combination via crosslinked alginate/lactoferrin nanohybrids for enhanced breast cancer treatment. Pharmaceutics 2022 14 11 2404 10.3390/pharmaceutics14112404 36365222
    [Google Scholar]
  128. Kanwar J. Kamalapuram S. Kanwar R. Roy K. Chaudhary R. Sehgal R. Theranostic multimodular potential of zinc-doped ferrite-saturated metal-binding protein-loaded novel nanocapsules in cancers. Int. J. Nanomedicine 2016 11 1349 1366 10.2147/IJN.S95253 27099495
    [Google Scholar]
  129. Sharifi M. Rezayat S.M. Akhtari K. Hasan A. Falahati M. Fabrication and evaluation of anti-cancer efficacy of lactoferrin-coated maghemite and magnetite nanoparticles. J. Biomol. Struct. Dyn. 2020 38 10 2945 2954 10.1080/07391102.2019.1650114 31354071
    [Google Scholar]
/content/journals/cdd/10.2174/0115672018351146250307083901
Loading
/content/journals/cdd/10.2174/0115672018351146250307083901
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test