title: Development of an anti-microbial peptide-mediated liposomal delivery system: a novel approach towards pH-responsive anti-microbial peptides.
abstract: On one hand, the application of anti-microbial peptides (AMPs) in the construction of AMPs-mediated drug delivery system has not yet been fully exploited; on the other hand, its non-selectivity in vivo has also limited its clinical application. In this work, we chose one pH-responsive peptide, [D]-H6L9, and functionalized it onto the surface of liposomes (D-Lip). The protonation of histidines in the sequence of [D]-H6L9 under pH 6.3 could switch the surface charge of D-Lip from negative (under pH 7.4) to positive (under pH 6.3), and the cellular uptake and tumor spheroids uptake were increased accordingly. Lysosome co-localization assay suggested that there was only little overlap of D-Lip with lysosomes in 12 h, which indicated that D-Lip could escape lysosomes effectively. In vivo biodistribution assay on C26 tumor-bearing BALB/C mice showed that DiR-labeled D-Lip could reach tumors as much as PEG-Lip, and both tumor slices and quantitative measurement of dispersed cells of in vivo tumors by flow cytometry demonstrated that D-Lip could be taken up by tumors more efficiently. Therefore, we have established an anti-microbial peptide-mediated liposomal delivery system for tumor delivery.
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Qianyu
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Ran
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Yayuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.affiliation: a Key Laboratory of Drug Targeting and Drug Delivery Systems , West China School of Pharmacy, Sichuan University , Chengdu , PR China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D023181:Antimicrobial Cationic Peptides; D008081:Liposomes; D009842:Oligopeptides; D011092:Polyethylene Glycols; D017239:Paclitaxel
keywords: AMPs; [D]-H6L9 peptide; liposome; tumor delivery