期刊
DRUG DELIVERY
卷 23, 期 7, 页码 2445-2456出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/10717544.2015.1008707
关键词
CD 13 targeted; drug delivery; liposomes; near-infrared two-photon photolysis; photo-sensitive peptides
资金
- National Natural Science Foundation of China [81202466, 81402874, 81102498]
- Important National Science & Technology Specific Projects of China [2012ZX09301003-001-009]
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-PEG(2000)-psCPP and DSPE-PEG(5000)-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 95nm, 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.
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