title: Enhanced therapeutic efficacy of iRGD-conjugated crosslinked multilayer liposomes for drug delivery.
abstract: Targeting nanoparticles by conjugating various specific ligands has shown potential therapeutic efficacy in nanomedicine. However, poor penetration of antitumor drugs into solid tumors remains a major obstacle. Here, we describe a targeting strategy for antitumor drug delivery by conjugating a crosslinked multilamellar liposomal vesicle (cMLV) formulation with a tumor-penetrating peptide, iRGD. The results showed that iRGD peptides could facilitate the binding and cellular uptake of drug-loaded cMLVs and consequently enhance the antitumor efficacy in breast tumor cells, including multidrug-resistant cells. Moreover, colocalization data revealed that iRGD-conjugated cMLVs (iRGD-cMLVs) entered cells via the clathrin-mediated pathway, followed by endosome-lysosome transport for efficient drug delivery. Finally, in vivo study indicated that iRGD-cMLVs could deliver anticancer drugs efficiently to mediate significant tumor suppression.
authors.affiliation: Mork Family Department of Chemical Engineering and Materials Science, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Yarong
authors.initials: Y
authors.lastname: Liu
authors.forename: Man
authors.initials: M
authors.lastname: Ji
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.forename: Kye-Il
authors.initials: KI
authors.lastname: Joo
authors.forename: Pin
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002966:Clathrin / Q000378:metabolism; D003432:Cross-Linking Reagents / Q000737:chemistry*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004705:Endocytosis / Q000187:drug effects; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008081:Liposomes; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D016896:Treatment Outcome
chemical_list: D002966:Clathrin; D003432:Cross-Linking Reagents; D008081:Liposomes; C569656:N-end cysteine peptide tumor-homing peptide; D009842:Oligopeptides; D004317:Doxorubicin