Oligodeoxynucleotide Acid Loaded, NGR-Peptide-Conjugated Polymeric Liposomes: In Vitro and In Vivo Evaluation

Abstract

NGR-peptide-conjugated polymeric liposome, NGR/liposome/PEI/ODN (NGR/LPD), was prepared with oligodeoxynucleotide (ODN) condensed with PEI at a N/P ratio of 10:1 and PEG-stabilized liposome composed of 94% POPC, 2% DDAB, 3% DSPEPEG- 2000 and 1% DSPE-PEG-2000-maleimide. Liposome/PEI/ODN (LPD) complexes could significantly reduce toxicity of PEI and also enhance uptake of ODN by MCF-7 breast cancer cells compared with naked ODN. It was found that the differences in apoptosis index between NGR/LPD and LPD group were significant (P < 0.05). Tumor tissue showed necrosis in high dose group of NGR/LPD (20 µ g ASODN). In comparison with control group, the levels of hTERT mRNA, hTERT protein as well as c-Myc protein in the NGR/LPD group were markedly lower (P < 0.05) and the level of Bcl-2 protein in the NGR/LPD group was significantly higher (P < 0.05). NGR/LPD had the function of targeting to tumor cells compared with LPD and could inhibit tumor cells growth compared with control group.