Development of cell-penetrating peptide-modified MPEG-PCL diblock copolymeric nanoparticles for systemic gene delivery

作者：Tanaka Ko; Kanazawa Takanori^*; Shibata Yasunori; Suda Yumiko; Fukuda Tsunehiko; Takashima Yuuki; Okada Hiroaki

来源：International Journal of Pharmaceutics, 2010, 396(1-2): 229-238.

DOI：10.1016/j.ijpharm.2010.06.028

• Block copolymeric nanoparticles
• Tat analog
• Disulfide linkage
• Polymer micelles
• Systemic non-viral gene carrier

To develop a safe and efficient systemic non-viral gene vector. methoxy poly(ethylene glycol) (MPEG)/poly(epsilon-caprolactone)(PCL) diblock copolymers conjugated with a Tat analog through the ester or disulfide linkage were synthesized and their suitability as a systemic non-viral gene carrier evaluated The physicochemical properties of the MPEG-PCL diblock copolymers were determined by GPC. (1)H NMR and FT-IR spectroscopy. The particle sizes and in vitro (COS7 and S-180 cells) transfection efficiencies and cytotoxicity were evaluated. Furthermore, the luciferase activity was then determined in various tissues after intravenous injection of MPEG-PCL-SS-Tat/pCMV-Luc complex into mice bearing S-180 cells. The particle sizes of the MPEG-PCL-Tat copolymers with or without pDNA were about 40 and 60 nm, respectively The luciferase activity in COS7 cells transfected with pCMV-Luc with MPEG-PCL-ester-Tat or MPEG-PCL-SS-Tat was higher than that with pDNA only MPEG-PCL-SS-Tat greatly increased the transfection efficiency compared to MPEG-PCL-ester-Tat in COS7 and S-180 cells In an in vitro cytotoxicity test MPEG-PCL-SS-Tat did not induce any remarkable cytotoxicity. In an in vivo experiment, the synthesized MPEG-PCL-SS-Tat copolymers promoted the delivery and expression of pDNA into tumor tissue in tumor-bearing mice.

• 出版日期2010-8-30