Studies on bioadhesive PLGA nanoparticles: A promising gene delivery system for efficient gene therapy to lung cancer.
Studies on bioadhesive PLGA nanoparticles: A promising gene delivery system for efficient gene therapy to lung cancer.
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DOI：
10.1016/j.ijpharm.2008.11.016
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发表时间：
2009-03
影响因子：
5.8
通讯作者：
W. Zou;Chunxi Liu;Zhijin Chen;N. Zhang
中科院分区：
文献类型：
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作者：
W. Zou;Chunxi Liu;Zhijin Chen;N. Zhang
该研究旨在设计新型生物粘附性PLGA纳米颗粒，用于有效地将基因递送至肺癌细胞。选择生物粘附剂和稳定剂Carbopol 940制备生物粘附性PLGA纳米粒，并制备Pluronic F68、Pluronic F127稳定的PLGA纳米粒作为对照。比较了不同表面活性剂对PLGA纳米粒理化性质和生物学特性的影响。与Lipofectamine 2000相比，所制备的纳米粒表面带负电荷，呈球形，粒径分布较窄，对A549细胞的毒性较低。Carbopol稳定的纳米颗粒在最佳Carbopol浓度下的DNA结合效率（>80%）、体外释放中DNA免受酶促降解的保护以及更好的缓冲能力方面具有优势。最重要的是，与Pluronics稳定的纳米颗粒或裸DNA相比，在A549细胞中观察到更高的转染效率，类似于Lipofectamine 2000。这些结果表明，与Carbopol配制的生物粘附性PLGA纳米粒可能是一个非常有吸引力的候选人，作为肺癌基因治疗的非病毒载体，并可能减轻传统的阳离子载体/DNA复合物用于体内基因递送的缺点。
The study aimed to design novel bioadhesive PLGA nanoparticles for efficient gene delivery to lung cancer cells. The bioadhesive agent and stabilizer, Carbopol 940 was chosen to establish bioadhesive PLGA nanoparticles and Pluronic F68, Pluronic F127 stabilized PLGA nanoparticles were formulated as control. The effects of different surfactants on the physicochemical and biological characterizations of PLGA nanoparticles were compared. All the obtained nanoparticles showed negative surface charge, similar spherical morphology, a relatively narrow particle size distribution, and lower cytotoxicity to A549 cells comparing with Lipofectamine 2000. Carbopol stabilized nanoparticles hold advantages in DNA-binding efficiency (>80%) at an optimal Carbopol concentration, DNA protection from enzymatic degradation in vitro release and better buffering capacity. Most importantly, higher transfection efficiency in A549 cells was observed comparing to Pluronics stabilized nanoparticles or naked DNA, similar to that of Lipofectamine 2000. These results revealed that the bioadhesive PLGA nanoparticles formulated with Carbopol might be a very attractive candidate as a non-viral vector for lung cancer gene therapy and might alleviate the drawbacks of the conventional cationic vectors/DNA complexes for gene delivery in vivo.