title: Targeted delivery of cargoes into a murine solid tumor by a cell-penetrating peptide and cleavable poly(ethylene glycol) comodified liposomal delivery system via systemic administration.
abstract: A liposomal delivery system with a high efficiency of accumulation in tumor tissue and then transportation of the cargo into tumor cells was developed here and evaluated via systemic administration. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-poly(ethylene glycol)(2000) (DSPE-PEG(2000))-TAT and protective DSPE-PEG(2000) modified liposomes possessing good stability in 50% FBS (fetal bovine serum) and good uptake efficiency were used as the basic formulation (TAT-SL; SL = stealth liposome), and then longer cysteine (Cys)-cleavable PEG(5000) was incorporated to modulate the function of TAT. All of the formulations to be used in vivo had sizes in a range of 80-100 nm and were stable in the presence of 50% FBS. Optical imaging showed that the incorporation of cleavable PEG(5000) into TAT-SL (i.e., C-TAT-SL) led to much more tumor accumulation and much less liver distribution compared with TAT-SL. The in vivo delivery profiles of C-TAT-SL were investigated using DiD as a fluorescent probe. Confocal laser scanning microscopy and flow cytometry showed that C-TAT-SL had a 48% higher (p < 0.001) delivery efficiency in the absence of Cys and a 130% higher (p < 0.001) delivery efficiency in the presence of Cys than the control (SL), indicating the successful targeted delivery of cargo was achieved by C-TAT-SL via systemic administration especially with a subsequent administration of Cys.
authors: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan, PR China.
authors: Rui
authors: R
authors: Kuai
authors: Wenmin
authors: W
authors: Yuan
authors: Wanyu
authors: W
authors: Li
authors: Yao
authors: Y
authors: Qin
authors: Jie
authors: J
authors: Tang
authors: Mingqing
authors: M
authors: Yuan
authors: Ling
authors: L
authors: Fu
authors: Rui
authors: R
authors: Ran
authors: Zhirong
authors: Z
authors: Zhang
authors: Qin
authors: Q
authors: He
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000235:genetics; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D005456:Fluorescent Dyes / Q000737:chemistry; D015696:Gene Products, tat / Q000737:chemistry* / Q000235:genetics; D007275:Injections, Intravenous; D008081:Liposomes / Q000737:chemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D005456:Fluorescent Dyes; D015696:Gene Products, tat; D008081:Liposomes; D011092:Polyethylene Glycols