Fabrication of Charge-Conversion Nanoparticles for Cancer Imaging by Flash Nanoprecipitation
2018
Li, Meng | Xu, Yisheng | Sun, Jinli | Wang, Mingwei | Yang, Dahai | Guo, Xuhong | Song, Haiyun | Cao, Song | Yan, Yunfeng
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.
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