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通过硼酸邻苯二酚酯键将抗癌药物硼替佐米(bortezomib,BTZ)连接到两亲型梳状聚衣康酸接枝共聚物(PIA-PEG-DDA-DPA)上,制备pH敏感型载药聚合物PIA-PEG-DDA-DPA-BTZ.通过核磁共振(NMR)表征了该聚合物的结构.DLS和AFM测试结果表明,该聚合物流体力学直径较小约为25~38 nm;芘荧光法测定表明,其临界胶束浓度(CMC)为2.54×10-3mg/mL.利用硼替佐米位于310 nm处的紫外特征吸收峰,分别在模拟生理pH值(7.4)及溶酶体和内涵体pH值(5.0)的条件下,研究聚合物的释药行为,结果表明,该体系在生理pH环境下基本无释药行为,在溶酶体和内涵体pH环境下,BTZ的累计释放率随时间变化曲线符合一级动力学方程Q=61.65866-62.13481e-0.32544t.相关的细胞实验表明,该种载药聚合物体系对癌细胞的抑制作用明显,接近硼替佐米纯品的效果.
The anticancer drug bortezomib (BTZ) was linked to the amphiphilic comb-like poly (itaconic acid) graft copolymer (PIA-PEG-DDA-DPA) via catechol borate bond to prepare pH-sensitive The structure of the polymer was characterized by nuclear magnetic resonance (NMR). The results of DLS and AFM showed that the diameter of the polymer was about 25 ~ 38 nm, Pyrene fluorescence method showed that the critical micelle concentration (CMC) was 2.54 × 10-3mg / mL. The characteristic absorption peak of bortezomib at 310 nm was observed at simulated physiological pH (7.4) and lysosome And the pH value of endosomes (5.0), the release behavior of the polymer was studied. The results showed that the system had no drug release behavior under physiological pH environment. The accumulation of BTZ in the lysosome and endosomal pH environment The curve of release rate with time conforms to the first-order kinetic equation Q = 61.65866-62.13481e-0.32544t. The related cell experiments show that the drug-loaded polymer system has obvious inhibitory effect on cancer cells and is close to the pure product of bortezomib effect.