Engineering Research Center of Xinjiang Bingtuan of Materials Chemical Engineering , Shihezi University , Shihezi 832000 , P. R. China.
School of Public Health , Shanghai Jiao Tong University , Shanghai 200025 , P. R. China.
ACS Appl Mater Interfaces. 2018 Apr 4;10(13):10752-10760. doi: 10.1021/acsami.8b01788. Epub 2018 Mar 20.
Traditional charge-conversion nanoparticles (NPs) need the breakage of acid-labile groups on the surface, which impedes the rapid response to the acidic microenvironment. Here, we developed novel rodlike charge-conversion NPs with amphiphilic dextran- b-poly(lactic- co-glycolic acid), poly(2-(dimethylamino) ethylmethylacrylate)- b-poly(ε-caprolactone), and an aggregation-induced emission-active probe through flash nanoprecipitation (FNP). These NPs exhibit reversible negative-to-positive charge transition at a slightly acidic pH relying on the rapid protonation/deprotonation of polymers. The size and the critical charge-conversion pH can be further tuned by varying the flow rate and polymer ratio. Consequently, the charge conversion endows NPs with resistance to protein adsorption at physiological pH and enhanced internalization to cancer cells under acidic conditions. Ex vivo imaging on harvest organs shows that charge-conversion NPs were predominantly distributed in tumors after intravenous administration to mice due to the robust response of NPs to the acidic microenvironment in tumor tissue, whereas control NPs or free probes were broadly accumulated in tumor, liver, kidney, and lung. These results suggest the great potential of the current FNP strategy in the facile and generic fabrication of charge-conversion NPs for tumor-targeting delivery of drugs or fluorescent probes.
传统的电荷转换纳米颗粒 (NPs) 需要表面上酸不稳定基团的断裂，这阻碍了对酸性微环境的快速响应。在这里，我们通过快速纳米沉淀 (FNP) 开发了具有两亲性葡聚糖-b-聚（乳酸-共-乙醇酸）、聚（2-（二甲氨基）乙基甲基丙烯酸酯）-b-聚（ε-己内酯）和聚集诱导发射活性探针的新型棒状电荷转换 NPs。这些 NPs 在略微酸性的 pH 值下表现出可逆的负到正电荷转换，这依赖于聚合物的快速质子化/去质子化。通过改变流速和聚合物比例，可以进一步调整尺寸和临界电荷转换 pH 值。因此，电荷转换使 NPs 在生理 pH 值下能够抵抗蛋白质吸附，并在酸性条件下增强对癌细胞的内化。在收获器官上的体外成像表明，在向小鼠静脉给药后，电荷转换 NPs 主要分布在肿瘤中，这是由于 NPs 对肿瘤组织中酸性微环境的强烈响应，而对照 NPs 或游离探针则广泛分布在肿瘤、肝脏、肾脏和肺部。这些结果表明，当前的 FNP 策略在用于药物或荧光探针的肿瘤靶向递药的简便通用的电荷转换 NPs 的制备方面具有巨大潜力。
