Ultrasound-Triggered Phase-Transition Cationic Nanodroplets for Enhanced Gene Delivery

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• 作者：Di Gao ; Ming Xu ; Zhong Cao ; Jinbiao Gao ; Ya Chen ; Yingqin Li ; Zhe Yang ; Xiaoyan Xie ; Qing Jiang ; Wei Wang ; Jie Liu
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2015
• 出版时间：June 24, 2015
• 年：2015
• 卷：7
• 期：24
• 页码：13524-13537
• 全文大小：690K
• ISSN：1944-8252

文摘

Ultrasound as an external stimulus for enhanced gene transfection represents a safe, noninvasive, cost-effective delivery strategy for gene therapy. Herein, we have developed an ultrasound-triggered phase-transition cationic nanodroplet based on a novel perfluorinated amphiphilic poly(amino acid), which could simultaneously load perfluoropentane (PFP) and nucleic acids. The heptadecafluoroundecylamine (C₁₁F₁₇-NH₂) was chosen to initiate 尾-benzyl-l-aspartate N-carboxyanhydride (BLA-NCA) ring-opening polymerization to prepare C₁₁F₁₇-poly(尾-benzyl-l-aspartate) (C₁₁F₁₇-PBLA). Subsequently, C₁₁F₁₇-poly{N-[N鈥?(2-aminoethyl)]aspartamide} [C₁₁F₁₇-PAsp(DET)] was synthesized by aminolysis reaction of C₁₁F₁₇-PBLA with diethylenetriamine (DET). PFP/pDNA-loaded nanodroplets PFP-TNDs [PFP/C₁₁F₁₇-PAsp(DET)/LucDNA/纬-PGA or poly(glutamic acid)-g-MeO-poly(ethylene glycol) (PGA-g-mPEG) ternary nanodroplets] were primarily formulated by an oil/water emulsification method, followed by surface modification with PGA-g-mPEG. The average diameter of PFP-TNDs ranged from 300 to 400 nm, and transmission electron microscopy images showed that the nanodroplets were nearly spherical in shape. The 味 potential of the nanodroplets dramatically decreased from +54.3 to +15.3 mV after modification with PGA-g-mPEG, resulting in a significant increase of the stability of the nanodroplets in the serum-containing condition. With ultrasound irradiation, the gene transfection efficiency was enhanced 14-fold on HepG2 cells, and ultrasound-triggered phase-transition cationic nanodroplets also displayed a good ultrasound contrast effect. These results suggest that the PFP/DNA-loaded phase-transition cationic nanodroplets can be utilized as efficient theranostic agents for targeting gene delivery.