title: A photo-responsive peptide- and asparagine-glycine-arginine (NGR) peptide-mediated liposomal delivery system.
abstract: The conjugation of tunable peptides or materials with nanocarriers represents a promising approach for drug delivery to tumor cells. In this study, we report the development of a novel liposomal carrier system that exploits the cell surface binding synergism between photo-sensitive peptides (PSPs) and targeting ligands. The positive charges of the lysine residues on the cell-penetrating peptides (CPPs) were temporarily caged by the photolabile-protective groups (PG), thereby forming a PSP. Furthermore, this PSP enhances specific uptake into cancer cells after rapidly uncaging the PG via near-infrared (NIR) light illumination. In the circulatory system, the cell penetrability of PSP was hindered. In contrast, the asparagine-glycine-arginine (NGR) peptide moieties, selectively bind to CD13-positive tumors, were attached to the nanocarrier to facilitate the active accumulation of this liposomal carrier in tumor tissue. The dual-modified liposomes (PSP/NGR-L) were prepared by emulsification method, and the concentrations of DSPE-PEG2000-psCPP and DSPE-PEG5000-NGR in the liposomes were chosen to be 4% and 1% (molar ratio), respectively. The mean particle size of the PSP/NGR-L was about 95 nm, and the drug entrapment efficiency was more than 90%. Cellular uptake results demonstrated that the proposed PSP/NGR-L had an enhancement of cancer cell recognition and specific uptake. Furthermore, the PSP/NGR-L demonstrated a stronger antitumor efficacy in the HT-1080 tumor model in nude mice with the aid of NIR illumination.
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , China.|b Wuhan General Hospital of Guangzhou Military Command , Wuhan , China , and.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , China.|c Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation , Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D057846:Cell-Penetrating Peptides / Q000008:administration & dosage* / Q000737:chemistry; D004337:Drug Carriers / Q000008:administration & dosage*; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008024:Ligands; D008081:Liposomes / Q000737:chemistry*; D061986:MCF-7 Cells; D051379:Mice; D036103:Nanotechnology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000528:radiation effects*; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000494:pharmacology
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D008024:Ligands; D008081:Liposomes; D009842:Oligopeptides; D010714:Phosphatidylethanolamines; C000615951:asparagine-glycine-arginine; C107570:polyethylene glycol-distearoylphosphatidylethanolamine; D011092:Polyethylene Glycols
keywords: CD 13 targeted; drug delivery; liposomes; near-infrared two-photon photolysis; photo-sensitive peptides