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2000
Volume 23, Issue 1
  • ISSN: 1567-2018
  • E-ISSN: 1875-5704

Abstract

The development of nanotechnology-based drug delivery systems has been extensively investigated across various therapies, leading to the creation of numerous nanomedicines for clinical use. However, these nanomedicines have yet to achieve the anticipated therapeutic efficacy in clinical settings, highlighting the urgent need for further research in this area. A primary challenge in nanomedicine research lies in ensuring that nanoparticles and therapeutic agents can effectively penetrate and accumulate within tumors. The enhanced permeability and retention (EPR) effect has been previously explored as a means to enhance drug delivery to tumors, but recent findings have revealed its limitations, including variable responses, restricted penetration, clearance by the reticuloendothelial system, and non-specific accumulation. As an alternative approach, transcytosis has been explored for delivering drugs to specific organs or tissues, potentially bypassing some of the constraints of the EPR effect. For example, nanoparticles can be guided through barriers by targeting specific receptors on cell surfaces or by utilizing a different charge compared to tumor cells' surfaces. Therefore, this article explores transcytosis, including adsorptive, receptor-mediated, and cell-mediated subtypes, all of which have demonstrated promising results and offer potential solutions to enhance the effectiveness of nanomedicine delivery for cancer therapy.

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References

  1. KhanI. SaeedK. KhanI. Nanoparticles: Properties, applications and toxicities.Arab. J. Chem.201912790893110.1016/j.arabjc.2017.05.011
     [Google Scholar]
  2. SunQ. ZhouZ. QiuN. ShenY. Rational design of cancer nanomedicine: Nanoproperty integration and synchronization.Adv. Mater.20172914160662810.1002/adma.20160662828234430
     [Google Scholar]
  3. DingS. KhanA.I. CaiX. SongY. LyuZ. DuD. DuttaP. LinY. Overcoming blood–brain barrier transport: Advances in nanoparticle-based drug delivery strategies.Mater. Today20203711212510.1016/j.mattod.2020.02.00133093794
     [Google Scholar]
  4. NakamuraY. MochidaA. ChoykeP.L. KobayashiH. Nanodrug delivery: Is the enhanced permeability and retention effect sufficient for curing cancer?Bioconjug. Chem.201627102225223810.1021/acs.bioconjchem.6b0043727547843
     [Google Scholar]
  5. PrabhakarU. MaedaH. JainR.K. Sevick-MuracaE.M. ZamboniW. FarokhzadO.C. BarryS.T. GabizonA. GrodzinskiP. BlakeyD.C. Challenges and key considerations of the enhanced permeability and retention effect for nanomedicine drug delivery in oncology.Cancer Res.20137382412241710.1158/0008‑5472.CAN‑12‑4561
     [Google Scholar]
  6. FungK.Y.Y. FairnG.D. LeeW.L. Transcellular vesicular transport in epithelial and endothelial cells: Challenges and opportunities.Traffic201819151810.1111/tra.1253328985008
     [Google Scholar]
  7. LiZ. ShanX. ChenZ. GaoN. ZengW. ZengX. MeiL. Applications of surface modification technologies in nanomedicine for deep tumor penetration.Adv. Sci. (Weinh.)202181200258910.1002/advs.20200258933437580
     [Google Scholar]
  8. SakhtianchiR. MinchinR.F. LeeK.B. AlkilanyA.M. SerpooshanV. MahmoudiM. Exocytosis of nanoparticles from cells: Role in cellular retention and toxicity.Adv. Colloid Interface Sci.2013201-202182910.1016/j.cis.2013.10.01324200091
     [Google Scholar]
  9. ZhouQ. DongC. FanW. JiangH. XiangJ. QiuN. PiaoY. XieT. LuoY. LiZ. LiuF. ShenY. Tumor extravasation and infiltration as barriers of nanomedicine for high efficacy: The current status and transcytosis strategy.Biomaterials202024011990210.1016/j.biomaterials.2020.11990232105817
     [Google Scholar]
  10. PawarB. VasdevN. GuptaT. MhatreM. MoreA. AnupN. TekadeR.K. Current update on transcellular brain drug delivery.Pharmaceutics20221412271910.3390/pharmaceutics1412271936559214
     [Google Scholar]
  11. AndreoneB.J. ChowB.W. TataA. LacosteB. Ben-ZviA. BullockK. DeikA.A. GintyD.D. ClishC.B. GuC. Blood-brain barrier permeability is regulated by lipid transport-dependent suppression of caveolae-mediated transcytosis.Neuron2017943581594.e510.1016/j.neuron.2017.03.04328416077
     [Google Scholar]
  12. ThuenauerR. MüllerS.K. RömerW. Pathways of protein and lipid receptor-mediated transcytosis in drug delivery.Expert Opin. Drug Deliv.201714334135110.1080/17425247.2016.122036427500785
     [Google Scholar]
  13. IzciM. MaksoudianC. ManshianB.B. SoenenS.J. The use of alternative strategies for enhanced nanoparticle delivery to solid tumors.Chem. Rev.202112131746180310.1021/acs.chemrev.0c0077933445874
     [Google Scholar]
  14. TorchilinV. Tumor delivery of macromolecular drugs based on the EPR effect.Adv. Drug Deliv. Rev.201163313113510.1016/j.addr.2010.03.01120304019
     [Google Scholar]
  15. ZiY. YangK. HeJ. WuZ. LiuJ. ZhangW. Strategies to enhance drug delivery to solid tumors by harnessing the EPR effects and alternative targeting mechanisms.Adv. Drug Deliv. Rev.202218811444910.1016/j.addr.2022.11444935835353
     [Google Scholar]
  16. SindhwaniS. SyedA.M. NgaiJ. KingstonB.R. MaiorinoL. RothschildJ. MacMillanP. ZhangY. RajeshN.U. HoangT. WuJ.L.Y. WilhelmS. ZilmanA. GaddeS. SulaimanA. OuyangB. LinZ. WangL. EgebladM. ChanW.C.W. The entry of nanoparticles into solid tumours.Nat. Mater.202019556657510.1038/s41563‑019‑0566‑231932672
     [Google Scholar]
  17. DasguptaA. SofiasA.M. KiesslingF. LammersT. Nanoparticle delivery to tumours: From EPR and ATR mechanisms to clinical impact.Nat. Rev. Bioeng.2024291310.1038/s44222‑024‑00203‑3
     [Google Scholar]
  18. PetrosR.A. DeSimoneJ.M. Strategies in the design of nanoparticles for therapeutic applications.Nat. Rev. Drug Discov.20109861562710.1038/nrd259120616808
     [Google Scholar]
  19. ZhaoJ. StenzelM.H. Entry of nanoparticles into cells: The importance of nanoparticle properties.Polym. Chem.20189325927210.1039/C7PY01603D
     [Google Scholar]
  20. LinX.P. MinternJ.D. GleesonP.A. Macropinocytosis in different cell types: Similarities and differences.Membranes (Basel)202010817710.3390/membranes1008017732756454
     [Google Scholar]
  21. Harush-FrenkelO. RozenturE. BenitaS. AltschulerY. Surface charge of nanoparticles determines their endocytic and transcytotic pathway in polarized MDCK cells.Biomacromolecules20089243544310.1021/bm700535p18189360
     [Google Scholar]
  22. DonahueN.D. AcarH. WilhelmS. Concepts of nanoparticle cellular uptake, intracellular trafficking, and kinetics in nanomedicine.Adv. Drug Deliv. Rev.2019143689610.1016/j.addr.2019.04.00831022434
     [Google Scholar]
  23. MulvihillJ.J.E. CunnaneE.M. RossA.M. DuskeyJ.T. TosiG. GrabruckerA.M. Drug delivery across the blood-brain barrier: Recent advances in the use of nanocarriers.Nanomedicine (Lond.)202015220521410.2217/nnm‑2019‑036731916480
     [Google Scholar]
  24. ZhouQ. LiJ. XiangJ. ShaoS. ZhouZ. TangJ. ShenY. Transcytosis-enabled active extravasation of tumor nanomedicine.Adv. Drug Deliv. Rev.202218911448010.1016/j.addr.2022.11448035952830
     [Google Scholar]
  25. YameenB. ChoiW.I. VilosC. SwamiA. ShiJ. FarokhzadO.C. Insight into nanoparticle cellular uptake and intracellular targeting.J. Control. Release201419048549910.1016/j.jconrel.2014.06.03824984011
     [Google Scholar]
  26. OzcanL. TabasI. Role of endoplasmic reticulum stress in metabolic disease and other disorders.Annu. Rev. Med.201263131732810.1146/annurev‑med‑043010‑14474922248326
     [Google Scholar]
  27. WangS. MaZ. XuX. WangZ. SunL. ZhouY. LinX. HongW. WangT. A role of Rab29 in the integrity of the trans-Golgi network and retrograde trafficking of mannose-6-phosphate receptor.PLoS One201495e9624210.1371/journal.pone.009624224788816
     [Google Scholar]
  28. QinM. ZhangJ. LiM. YangD. LiuD. SongS. FuJ. ZhangH. DaiW. WangX. WangY. HeB. ZhangQ. Proteomic analysis of intracellular protein corona of nanoparticles elucidates nano-trafficking network and nano-bio interactions.Theranostics20201031213122910.7150/thno.3890031938061
     [Google Scholar]
  29. SimionescuM. PopovD. SimaA. Endothelial transcytosis in health and disease.Cell Tissue Res.20093351274010.1007/s00441‑008‑0688‑318836747
     [Google Scholar]
  30. WileyD.T. WebsterP. GaleA. DavisM.E. Transcytosis and brain uptake of transferrin-containing nanoparticles by tuning avidity to transferrin receptor.Proc. Natl. Acad. Sci. USA2013110218662866710.1073/pnas.130715211023650374
     [Google Scholar]
  31. ZhangW. LiuQ.Y. HaqqaniA.S. LeclercS. LiuZ. FauteuxF. BaumannE. DelaneyC.E. LyD. StarA.T. BrunetteE. SodjaC. HewittM. SandhuJ.K. StanimirovicD.B. Differential expression of receptors mediating receptor-mediated transcytosis (RMT) in brain microvessels, brain parenchyma and peripheral tissues of the mouse and the human.Fluids Barriers CNS20201714710.1186/s12987‑020‑00209‑032698806
     [Google Scholar]
  32. PardridgeW.M. Kinetics of Blood–Brain Barrier Transport of Monoclonal Antibodies Targeting the Insulin Receptor and the Transferrin Receptor.Pharmaceuticals (Basel)2021151310.3390/ph1501000335056060
     [Google Scholar]
  33. ClarkeE. SinclairL. FletcherE.J. Krawczun-RygmaczewskaA. DutyS. StockiP. RutowskiJ.L. DohertyD.L. WalshF.S. A single domain shark antibody targeting the transferrin receptor 1 delivers a TrkB agonist antibody across the blood brain barrier to provide full neuroprotection in a mouse model of Parkinson’s Disease.bioRxiv20202020.0310.1101/2020.03.12.987313
     [Google Scholar]
  34. DubeyS.K. LakshmiK.K. KrishnaK.V. AgrawalM. SinghviG. SahaR.N. SarafS. SarafS. ShuklaR. AlexanderA. Insulin mediated novel therapies for the treatment of Alzheimer’s disease.Life Sci.202024911754010.1016/j.lfs.2020.11754032165212
     [Google Scholar]
  35. LeeJ.H. JahrlingJ.B. DennerL. DineleyK.T. Targeting insulin for Alzheimer’s disease: Mechanisms, status and potential directions.J. Alzheimers Dis.201864s1S427S45310.3233/JAD‑17992329710715
     [Google Scholar]
  36. LiH. GongQ. LuoK. Biomarker-driven molecular imaging probes in radiotherapy.Theranostics202414104127414610.7150/thno.9776838994026
     [Google Scholar]
  37. ChangJ. PaillardA. PassiraniC. MorilleM. BenoitJ.P. BetbederD. GarcionE. Transferrin adsorption onto PLGA nanoparticles governs their interaction with biological systems from blood circulation to brain cancer cells.Pharm. Res.20122961495150510.1007/s11095‑011‑0624‑122167349
     [Google Scholar]
  38. ClarkA.J. DavisM.E. Increased brain uptake of targeted nanoparticles by adding an acid-cleavable linkage between transferrin and the nanoparticle core.Proc. Natl. Acad. Sci. USA201511240124861249110.1073/pnas.151704811226392563
     [Google Scholar]
  39. RuanS. QinL. XiaoW. HuC. ZhouY. WangR. SunX. YuW. HeQ. GaoH. Acid-responsive transferrin dissociation and GLUT mediated exocytosis for increased blood–brain barrier transcytosis and programmed glioma targeting delivery.Adv. Funct. Mater.20182830180222710.1002/adfm.201802227
     [Google Scholar]
  40. QiaoC. YangJ. ShenQ. LiuR. LiY. ShiY. ChenJ. ShenY. XiaoZ. WengJ. ZhangX. Traceable nanoparticles with dual targeting and ROS response for RNAi‐based immunochemotherapy of intracranial glioblastoma treatment.Adv. Mater.20183018170505410.1002/adma.20170505429577457
     [Google Scholar]
  41. ReginaA. DemeuleM. TripathyS. Lord-DufourS. CurrieJ.C. IddirM. AnnabiB. CastaigneJ.P. LachowiczJ.E. ANG4043, a novel brain-penetrant peptide-mAb conjugate, is efficacious against HER2-positive intracranial tumors in mice.Mol. Cancer Ther.201514112914010.1158/1535‑7163.MCT‑14‑039925492620
     [Google Scholar]
  42. LiH. QianZ.M. Transferrin/transferrin receptor‐mediated drug delivery.Med. Res. Rev.200222322525010.1002/med.1000811933019
     [Google Scholar]
  43. KawabataH. Transferrin and transferrin receptors update.Free Radic. Biol. Med.2019133465410.1016/j.freeradbiomed.2018.06.03729969719
     [Google Scholar]
  44. MatsuiM. SakuraiF. ElbashirS. FosterD.J. ManoharanM. CoreyD.R. Activation of LDL receptor expression by small RNAs complementary to a noncoding transcript that overlaps the LDLR promoter.Chem. Biol.201017121344135510.1016/j.chembiol.2010.10.00921168770
     [Google Scholar]
  45. ShenG.Q. LiL. GirelliD. SeidelmannS.B. RaoS. FanC. ParkJ.E. XiQ. LiJ. HuY. OlivieriO. MarchantK. BarnardJ. CorrocherR. ElstonR. CassanoJ. HendersonS. HazenS.L. PlowE.F. TopolE.J. WangQ.K. An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction.Am. J. Hum. Genet.200781478079110.1086/52158117847002
     [Google Scholar]
  46. von WolffM. UrselS. HahnU. SteldingerR. StrowitzkiT. Glucose transporter proteins (GLUT) in human endometrium: Expression, regulation, and function throughout the menstrual cycle and in early pregnancy.J. Clin. Endocrinol. Metab.20038883885389210.1210/jc.2002‑02189012915684
     [Google Scholar]
  47. KorgunE.T. Celik-OzenciC. SevalY. DesoyeG. DemirR. Do glucose transporters have other roles in addition to placental glucose transport during early pregnancy?Histochem. Cell Biol.2005123662162910.1007/s00418‑005‑0792‑315965666
     [Google Scholar]
  48. YehW.L. LinC.J. FuW.M. Enhancement of glucose transporter expression of brain endothelial cells by vascular endothelial growth factor derived from glioma exposed to hypoxia.Mol. Pharmacol.200873117017710.1124/mol.107.03885117942749
     [Google Scholar]
  49. ChaudharyB. KhaledY.S. AmmoriB.J. ElkordE. Neuropilin 1: Function and therapeutic potential in cancer.Cancer Immunol. Immunother.2014632819910.1007/s00262‑013‑1500‑024263240
     [Google Scholar]
  50. LiuS.D. ZhongL.P. HeJ. ZhaoY.X. Targeting neuropilin-1 interactions is a promising anti-tumor strategy.Chin. Med. J. (Engl.)2021134550851710.1097/CM9.000000000000120033177389
     [Google Scholar]
  51. MiaoH.Q. LeeP. LinH. SokerS. KlagsbrunM. Neuropilin‐1 expression by tumor cells promotes tumor angiogenesis and progression.FASEB J.200014152532253910.1096/fj.00‑0250com11099472
     [Google Scholar]
  52. MützeJ. RothJ. GerstbergerR. MatsumuraK. HübschleT. Immunohistochemical evidence of functional leptin receptor expression in neuronal and endothelial cells of the rat brain.Neurosci. Lett.2006394210511010.1016/j.neulet.2005.10.03116289843
     [Google Scholar]
  53. CanteroD. FriessH. DeflorinJ. ZimmermannA. BründlerM-A. RiesleE. KorcM. BüchlerM.W. Enhanced expression of urokinase plasminogen activator and its receptor in pancreatic carcinoma.Br. J. Cancer199775338839510.1038/bjc.1997.639020484
     [Google Scholar]
  54. DiLuciaS.G. KendrickB.J. Sims-RobinsonC. Hyperinsulinemia impairs clathrin-mediated endocytosis of the insulin receptor and activation of endothelial nitric oxide synthase in brain endothelial cells.Int. J. Mol. Sci.202324191467010.3390/ijms24191467037834116
     [Google Scholar]
  55. SoniU.K. JennyL. HegdeR.S. IGF-1R targeting in cancer – Does sub-cellular localization matter?J. Exp. Clin. Cancer Res.202342127310.1186/s13046‑023‑02850‑737858153
     [Google Scholar]
  56. MartinsA.S. OrdóñezJ.L. AmaralA.T. PrinsF. FlorisG. Debiec-RychterM. HogendoornP.C.W. de AlavaE. IGF1R signaling in Ewing sarcoma is shaped by clathrin-/caveolin-dependent endocytosis.PLoS One201165e1984610.1371/journal.pone.001984621611203
     [Google Scholar]
  57. SongX. LiR. DengH. LiY. CuiY. ZhangH. DaiW. HeB. ZhengY. WangX. ZhangQ. Receptor mediated transcytosis in biological barrier: The influence of receptor character and their ligand density on the transmembrane pathway of active-targeting nanocarriers.Biomaterials2018180789010.1016/j.biomaterials.2018.07.00630025247
     [Google Scholar]
  58. LuW. Adsorptive-mediated brain delivery systems.Curr. Pharm. Biotechnol.201213122340234810.2174/13892011280334185123016640
     [Google Scholar]
  59. KucharzK. KutuzovN. ZhukovO. Mathiesen JaniurekM. LauritzenM. Shedding light on the Blood–Brain barrier transport with Two-Photon microscopy in vivo.Pharm. Res.20223971457146810.1007/s11095‑022‑03266‑235578062
     [Google Scholar]
  60. ChackoJ.B. JoseS. Chapter 9 - PLGA-based nanoparticles for treatment of cerebral diseases.Poly(lactic-co-glycolic acid) (PLGA) Nanoparticles for Drug DeliveryElsevier202323526610.1016/B978‑0‑323‑91215‑0.00018‑2
     [Google Scholar]
  61. ZhouQ. ShaoS. WangJ. XuC. XiangJ. PiaoY. ZhouZ. YuQ. TangJ. LiuX. GanZ. MoR. GuZ. ShenY. Enzyme-activatable polymer–drug conjugate augments tumour penetration and treatment efficacy.Nat. Nanotechnol.201914879980910.1038/s41565‑019‑0485‑z31263194
     [Google Scholar]
  62. SuzukiH. BaeY.H. Evaluation of drug penetration with cationic micelles and their penetration mechanism using an in vitro tumor model.Biomaterials20169812013010.1016/j.biomaterials.2016.04.03727182814
     [Google Scholar]
  63. LiJ. KataokaK. Chemo-physical strategies to advance the in vivo functionality of targeted nanomedicine: The next generation.J. Am. Chem. Soc.2021143253855910.1021/jacs.0c0902933370092
     [Google Scholar]
  64. ChenS. ZhongY. FanW. XiangJ. WangG. ZhouQ. WangJ. GengY. SunR. ZhangZ. PiaoY. WangJ. ZhuoJ. CongH. JiangH. LingJ. LiZ. YangD. YaoX. XuX. ZhouZ. TangJ. ShenY. Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion–drug conjugates with cell-membrane affinity.Nat. Biomed. Eng.2021591019103710.1038/s41551‑021‑00701‑433859387
     [Google Scholar]
  65. LalatsaA. SchatzleinA.G. UchegbuI.F. Strategies to deliver peptide drugs to the brain.Mol. Pharm.20141141081109310.1021/mp400680d24601686
     [Google Scholar]
  66. Hasannejad-AslB. PooresmaeilF. TakamoliS. DabiriM. BolhassaniA. Cell penetrating peptide: A potent delivery system in vaccine development.Front. Pharmacol.202213107268510.3389/fphar.2022.107268536425579
     [Google Scholar]
  67. LuW. ZhangY. TanY.Z. HuK.L. JiangX.G. FuS.K. Cationic albumin-conjugated pegylated nanoparticles as novel drug carrier for brain delivery.J. Control. Release2005107342844810.1016/j.jconrel.2005.03.02716176844
     [Google Scholar]
  68. ArvizoR.R. MirandaO.R. MoyanoD.F. WaldenC.A. GiriK. BhattacharyaR. RobertsonJ.D. RotelloV.M. ReidJ.M. MukherjeeP. Modulating pharmacokinetics, tumor uptake and biodistribution by engineered nanoparticles.PLoS One201169e2437410.1371/journal.pone.002437421931696
     [Google Scholar]
  69. SchwartzS. Unmet needs in developing nanoparticles for precision medicine.Nanomedicine (Lond)201712427127410.2217/nnm‑2016‑039028093937
     [Google Scholar]
  70. SukJ.S. XuQ. KimN. HanesJ. EnsignL.M. PEGylation as a strategy for improving nanoparticle-based drug and gene delivery.Adv. Drug Deliv. Rev.201699Pt A285110.1016/j.addr.2015.09.01226456916
     [Google Scholar]
  71. AliI.U. ChenX. Penetrating the blood–brain barrier: Promise of novel nanoplatforms and delivery vehicles.ACS Nano20159109470947410.1021/acsnano.5b0534126406936
     [Google Scholar]
  72. ChengY. MorshedR. ChengS.H. TobiasA. AuffingerB. WainwrightD.A. ZhangL. YunisC. HanY. ChenC.T. LoL.W. AboodyK.S. AhmedA.U. LesniakM.S. Nanoparticle-programmed self-destructive neural stem cells for glioblastoma targeting and therapy.Small20139244123412910.1002/smll.20130111123873826
     [Google Scholar]
  73. XueJ. ZhaoZ. ZhangL. XueL. ShenS. WenY. WeiZ. WangL. KongL. SunH. PingQ. MoR. ZhangC. Neutrophil-mediated anticancer drug delivery for suppression of postoperative malignant glioma recurrence.Nat. Nanotechnol.201712769270010.1038/nnano.2017.5428650441
     [Google Scholar]
  74. WuM. ZhangH. TieC. YanC. DengZ. WanQ. LiuX. YanF. ZhengH. MR imaging tracking of inflammation-activatable engineered neutrophils for targeted therapy of surgically treated glioma.Nat. Commun.201891477710.1038/s41467‑018‑07250‑630429468
     [Google Scholar]
  75. KhatamiS.H. KaramiN. Taheri-AnganehM. TaghvimiS. TondroG. KhorsandM. Soltani FardE. SedighimehrN. KazemiM. Rahimi JaberiK. MoradiM. Nafisi FardP. DarvishiM.H. MovahedpourA. Exosomes: Promising delivery tools for overcoming blood-brain barrier and glioblastoma therapy.Mol. Neurobiol.20236084659467810.1007/s12035‑023‑03365‑037138197
     [Google Scholar]
  76. RehmanF.U. LiuY. ZhengM. ShiB. Exosomes based strategies for brain drug delivery.Biomaterials202329312194910.1016/j.biomaterials.2022.12194936525706
     [Google Scholar]
  77. BorG. Hosta-RigauL. Next generation of brain cancer nanomedicines to overcome the Blood–Brain Barrier (BBB): Insights on transcytosis, perivascular tumor growth, and BBB models.Adv. Ther. (Weinh.)2023612230016110.1002/adtp.202300161
     [Google Scholar]
  78. KimR. LeeS. LeeJ. KimM. KimW.J. LeeH.W. LeeM.Y. KimJ. ChangW. Exosomes derived from microRNA-584 transfected mesenchymal stem cells: Novel alternative therapeutic vehicles for cancer therapy.BMB Rep.201851840641110.5483/BMBRep.2018.51.8.10529966581
     [Google Scholar]
  79. VaderP. MolE.A. PasterkampG. SchiffelersR.M. Extracellular vesicles for drug delivery.Adv. Drug Deliv. Rev.2016106Pt A14815610.1016/j.addr.2016.02.00626928656
     [Google Scholar]
  80. MoradG. CarmanC.V. HagedornE.J. PerlinJ.R. ZonL.I. MustafaogluN. ParkT.E. IngberD.E. DaisyC.C. MosesM.A. Tumor-derived extracellular vesicles breach the intact blood–brain barrier via transcytosis.ACS Nano20191312138531386510.1021/acsnano.9b0439731479239
     [Google Scholar]
  81. ZhuX. JinK. HuangY. PangZ. Brain drug delivery by adsorption-mediated transcytosis.Brain Targeted Drug Delivery System.Elsevier201915918310.1016/B978‑0‑12‑814001‑7.00007‑X
     [Google Scholar]
  82. VyasS.P. SinghA. SihorkarV. Ligand-receptor-mediated drug delivery: An emerging paradigm in cellular drug targeting.Crit. Rev. Ther. Drug Carrier Syst.200118117610.1615/CritRevTherDrugCarrierSyst.v18.i1.1011326743
     [Google Scholar]
  83. LukB.T. ZhangL. Cell membrane-camouflaged nanoparticles for drug delivery.J. Control. Release2015220Pt B60060710.1016/j.jconrel.2015.07.01926210440
     [Google Scholar]
  84. Bohn ThomsenL. LichotaJ. Navndrup EskehaveT. LinemannT. Hog MortensenJ. Gaarn du JardinK. MoosT. Brain delivery systems via mechanism independent of receptor-mediated endocytosis and adsorptive-mediated endocytosis.Curr. Pharm. Biotechnol.201213122349235410.2174/13892011280334184223016641
     [Google Scholar]
  85. KumarV. FarellG. YuS. HarringtonS. FitzpatrickL. RzewuskaE. MillerV.M. LieskeJ.C. Cell biology of pathologic renal calcification: Contribution of crystal transcytosis, cell-mediated calcification, and nanoparticles.J. Investig. Med.200654741242410.2310/6650.2006.0602117169263
     [Google Scholar]
  86. HansenS.H. SandvigK. van DeursB. Molecules internalized by clathrin-independent endocytosis are delivered to endosomes containing transferrin receptors.J. Cell Biol.19931231899710.1083/jcb.123.1.898408209
     [Google Scholar]
  87. FillebeenC. DescampsL. DehouckM.P. FenartL. BenaïssaM. SpikG. CecchelliR. PierceA. Receptor-mediated transcytosis of lactoferrin through the blood-brain barrier.J. Biol. Chem.1999274117011701710.1074/jbc.274.11.701110066755
     [Google Scholar]
  88. AziziP.M. ZylaR.E. GuanS. WangC. LiuJ. BolzS.S. HeitB. KlipA. LeeW.L. Clathrin-dependent entry and vesicle-mediated exocytosis define insulin transcytosis across microvascular endothelial cells.Mol. Biol. Cell201526474075010.1091/mbc.E14‑08‑130725540431
     [Google Scholar]
  89. HansenC.G. NicholsB.J. Molecular mechanisms of clathrin-independent endocytosis.J. Cell Sci.2009122111713172110.1242/jcs.03395119461071
     [Google Scholar]
  90. GeorgievaJ. HoekstraD. ZuhornI. Smuggling drugs into the brain: An overview of ligands targeting transcytosis for drug delivery across the blood–brain barrier.Pharmaceutics20146455758310.3390/pharmaceutics604055725407801
     [Google Scholar]
  91. ChoudhuryH. PandeyM. ChinP.X. PhangY.L. CheahJ.Y. OoiS.C. MakK.K. PichikaM.R. KesharwaniP. HussainZ. GorainB. Transferrin receptors-targeting nanocarriers for efficient targeted delivery and transcytosis of drugs into the brain tumors: a review of recent advancements and emerging trends.Drug Deliv. Transl. Res.2018851545156310.1007/s13346‑018‑0552‑229916012
     [Google Scholar]
  92. XuQ. YanX. ZhangY. WuJ. Current understanding of transport and bioavailability of bioactive peptides derived from dairy proteins: a review.Int. J. Food Sci. Technol.20195461930194110.1111/ijfs.14055
     [Google Scholar]
  93. YangA.C. StevensM.Y. ChenM.B. LeeD.P. StähliD. GateD. ContrepoisK. ChenW. IramT. ZhangL. VestR.T. ChaneyA. LehallierB. OlssonN. du BoisH. HsiehR. CropperH.C. BerdnikD. LiL. WangE.Y. TraberG.M. BertozziC.R. LuoJ. SnyderM.P. EliasJ.E. QuakeS.R. JamesM.L. Wyss-CorayT. Physiological blood–brain transport is impaired with age by a shift in transcytosis.Nature2020583781642543010.1038/s41586‑020‑2453‑z32612231
     [Google Scholar]
  94. MuroS. KovalM. MuzykantovV. Endothelial endocytic pathways: Gates for vascular drug delivery.Curr. Vasc. Pharmacol.20042328129910.2174/157016104338573615320826
     [Google Scholar]
  95. HervéF. GhineaN. ScherrmannJ.M. CNS delivery via adsorptive transcytosis.AAPS J.200810345547210.1208/s12248‑008‑9055‑218726697
     [Google Scholar]
  96. OdomT.L. LeBrocH.D. CallmannC.E. Biomacromolecule-tagged nanoscale constructs for crossing the blood–brain barrier.Nanoscale20241683969397610.1039/D3NR06154J38305381
     [Google Scholar]
  97. WangG. WuB. LiQ. ChenS. JinX. LiuY. ZhouZ. ShenY. HuangP. Active transportation of liposome enhances tumor accumulation, penetration, and therapeutic efficacy.Small20201644200417210.1002/smll.20200417233030305
     [Google Scholar]
  98. JiaF. LiL. FangY. SongM. ManJ. JinQ. LeiY. JiJ. Macromolecular platform with super-cation enhanced trans-cornea infiltration for noninvasive nitric oxide delivery in ocular therapy.ACS Nano20201412169291693810.1021/acsnano.0c0597733289535
     [Google Scholar]
  99. LiZ. ZhangQ. LiZ. RenL. PanD. GongQ. GuZ. CaiH. LuoK. Branched glycopolymer prodrug-derived nanoassembly combined with a STING agonist activates an immuno-supportive status to boost anti-PD-L1 antibody therapy.Acta Pharm. Sin. B20241452194220910.1016/j.apsb.2024.02.00638799622
     [Google Scholar]
  100. PanditS. DuttaD. NieS. Active transcytosis and new opportunities for cancer nanomedicine.Nat. Mater.202019547848010.1038/s41563‑020‑0672‑132332990
     [Google Scholar]
/content/journals/cdd/10.2174/0115672018336038240930082554
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Nanoparticle-Mediated Transcytosis in Tumor Drug Delivery: Mechanisms, Categories, and Novel Applications
Curr. Drug Deliv. 23, 73 (2026); https://doi.org/10.2174/0115672018336038240930082554
/content/journals/cdd/10.2174/0115672018336038240930082554
/content/journals/cdd/10.2174/0115672018336038240930082554
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  • Article Type:     Review Article
Keyword(s): adsorptive-mediated transcytosis; cell-mediated transcytosis; drug delivery system; enhanced permeability and retention effect; receptor-mediated transcytosis; transcytosis; Tumor

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