以壳聚糖为基质的智能电荷翻转体系用于紫杉醇的高效输送

Chitosan-based Intelligent Charge-reversed System for High Efficiency Delivery of Paclitaxel

通过在羧甲基壳聚糖纳米球(CNP)表面修饰三(2-氨基乙基)胺(TAEA)及2,3-二甲基马来酸酐(DMMA),得到针对肿瘤微酸环境响应的智能电荷翻转体系(CNP:TAEA:DMMA纳米球),并用于难溶性抗肿瘤药物紫杉醇(PTX)的高效输送.结果表明,所制纳米球在正常体液(pH7.4)条件下能保留其负电性(11mV),从而减少被巨噬细胞J774A.1摄取;而在肿瘤部位的微酸环境(pH6.8)下,其表面负电性(34.8mV)可迅速转化为正电性(+5mV),促进被肿瘤细胞LLC摄取,提高肿瘤细胞内的药物浓度.与市售注射剂相比,纳米球展现出良好的生物相容性,对肿瘤细胞杀伤效果也明显提高,其半抑制浓度从11.3降低至4.09g/mL,实现了PTX的高效输送.

After modification by tris（2-aminoethyl） amine （TAEA） and 2,3-dimethylmaleic anhydride （DMMA）, chitosan nanoparticles （CNP） were endowed with intelligent charge-reversal ability. The fabricated system （CNP-TAEA-DMMA- nanoparticles） was then loaded with insoluble anticancer drug paclitaxel （PTX）, and the drug delivery efficiency was tested in vivo. The results showed that PTX-CNP-TAEA-DMMA- nanoparticles were negatively charged （-11 mV） at normal tissue circumstance （pH 7.4） and rarely internalized by J774.1 cells, exhibiting stealth effect to macrophages. Once reaching the cancer site, those nanoparticles could intelligently transform to positive charge （＋5 mV） by the low-pH microenvironment in tumor tissue, which could improve tumor cell uptake and accordingly increase the drug concentration at the lesion site. Compared with commercial PTX formulation, the nanoparticles possessed superior biocompatibility and better cytotoxicity （the value of half inhibitory concentration was decreased to 4.09 from 11.3 μg/mL）, holding a great potential as efficient anti-cancer drug carrier.