title: Dual-functionalized liposomal delivery system for solid tumors based on RGD and a pH-responsive antimicrobial peptide.
abstract: [D]-H6L9, as a pH-responsive anti-microbial peptide (AMP), has been evidenced by us to be an excellent choice in tumor microenvironment-responsive delivery as it could render liposomes responsive to the acidified tumor microenvironment. However, [D]-H6L9-modified liposomes could not actively target to tumor area. Therefore, integrin αvβ3-targeted peptide RGD was co-modified with [D]-H6L9 onto liposomes [(R + D)-Lip] for improved tumor delivery efficiency. Under pH 6.3, (R + D)-Lip could be taken up by C26 cells and C26 tumor spheroids (integrin αvβ3-positive) with significantly improved efficiency compared with other groups, which was contributed by both RGD and [D]-H6L9, while RGD did not increase the cellular uptake performance on MCF-7 cells (integrin αvβ3-negative). Results showed that RGD could decrease cellular uptake of (R + D)-Lip while [D]-H6L9 could increase it, implying the role of both RGD and [D]-H6L9 in cellular internalization of (R + D)-Lip. On the other hand, (R + D)-Lip could escape the entrapment of lysosomes. PTX-loaded (R + D)-Lip could further increase the cellular toxicity against C26 cells compared with liposomes modified only with RGD and [D]-H6L9 respectively, and achieve remarkable tumor inhibition effect on C26 tumor models.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Qianyu
authors: Q
authors: Zhang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Libao
authors: L
authors: Lu
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Li
authors: L
authors: Zhang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Kairong
authors: K
authors: Shi
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Xingli
authors: X
authors: Cun
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Yuting
authors: Y
authors: Yang
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Yayuan
authors: Y
authors: Liu
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Huile
authors: H
authors: Gao
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, West China School of Pharmacy, Sichuan University, No. 17, Block 3, Southern RenminRoad, Chengdu 610041, China.
authors: Qin
authors: Q
authors: He
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D059016:Tumor Microenvironment
chemical_list: D023181:Antimicrobial Cationic Peptides; D000972:Antineoplastic Agents, Phytogenic; D039302:Integrin alphaVbeta3; D008081:Liposomes; D009842:Oligopeptides; D011092:Polyethylene Glycols; C047981:arginyl-glycyl-aspartic acid; D017239:Paclitaxel