pH/近红外光双响应卡培他滨智能印迹材料的制备及药物释放研究

以广谱抗癌药物卡培他滨(capecitabine,CAP)为模板,上转换纳米粒子为载体,3,5-二羧基-4-甲基丙烯酸酯偶氮苯和丙烯酸官能化明胶为双官能单体,N,N′-亚甲基双丙烯酰胺为交联剂,过硫酸铵为引发剂,采用表面聚合及分子印迹技术制备了具有pH值/近红外光双响应性能的纳米智能药物载体CAP-MIP(capecitabine-imprinted polymers)。实验结果表明,CAP-MIP不仅具有较好的载药活性(吸附容量7.00 mg/g),而且还具有良好的吸附选择性(CAP选择性因子α为2.904)。当介质pH分别为1.2、6.8和8.3时,CAP的最大累积释放率分别为1.71%、41.84%和89.54%,药物释放的平衡时间分别为40 min、180 min和420 min。当介质pH为6.8,且伴有近红外光(λ=980 nm)照射时,目标材料仅180 min就能使CAP达到最大累积释放率96.21%。此外,CAP-MIP还具有良好的稳定性,经过7次吸附-解吸循环后,CAP-MIP载药量损失率仅为8.29%。

Development of NIR-II fluorescence image-guided and pH-responsive nanocapsules for cocktail drug delivery

Nanocapsule-based targeted delivery and stimulus-responsive release can increase drug effectiveness, while reducing the side effects of the drug. However, difficulties in the scale-up synthesis, fast burst release, and low degradability, could hamper the translation of drug nanocapsules from lab to clinic. Here we have controllably functionalized the biodegradable and widely available polysuccinimide, in order to obtain an amphiphilic poly（amino acid）. Using this polymer, we designed nanocapsules （〈 100 nm） for hydrophobic drug delivery, which could facilitate tumor targeting, hydrogen bond-based pH-responsive release, and real-time fluorescence tracking, in the second near-infrared region. This method is versatile, eco-friendly, and easy to scale up at low costs. In addition, this system can carry a cocktail of drugs, obtained by loading multiple anticancer drugs to the same vehicle. Our nanocapsules were observed to be stable in blood vessels （pH = 7.4）, and the pH-responsive release （pH = 5.0 in lysosome） was sustained. The chemotherapy results in tumor-xenografted mice suggested that our nanocapsule was safe and efficient, and may be a useful tool for drug delivery.