Su Ting, Cheng Furong, Lin Shuibin, Xiao Tao, Zhu Yutong, Cao Jun, He Bin
Center for Translational Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, People's Republic of China.
ACS Appl Bio Mater. 2018 Oct 15;1(4):954-960. doi: 10.1021/acsabm.8b00355. Epub 2018 Sep 19.
Conventional photodynamic therapy used for cancer treatment is incapable of achieving satisfactory therapeutic effects because of a low encapsulation efficiency and uncontrolled photosensitizer leakage. Herein, we introduce a novel nanoparticle system with reduction-induced decomposition and photosensitizer self-aggregation capability to upregulate reactive oxygen species (ROS) level under UV irradiation in cancer cells, leading to cancer cells apoptosis. The nanoparticles could be self-assembled with low critical micellar concentration using amphiphilic polymers composed of polyethylene glycol segment and a bis(pyrene) molecule with a disulfide bond as a reduction linker. The HNMR and transmission electron microscopy results showed that the responsive disulfide bonds in the nanoparticles were specifically cleaved in the reductive environment, which resulted in in situ self-aggregation of the pyrene residues, which was confirmed by the results of UV and fluorescence spectra. Furthermore, confocal laser microscopy and flow cytometry demonstrated that the ROS level was upregulated in cancer cells exposed to nanoparticles under UV irradiation compared to insensitive group, causing cells apoptosis. Therefore, this strategy opens a new method for cancer therapy.
用于癌症治疗的传统光动力疗法由于包封效率低和光敏剂泄漏不受控制而无法取得令人满意的治疗效果。在此，我们引入了一种具有还原诱导分解和光敏剂自聚集能力的新型纳米粒子系统，以在紫外线照射下上调癌细胞中的活性氧（ROS）水平，从而导致癌细胞凋亡。使用由聚乙二醇链段和具有二硫键作为还原连接基的双（芘）分子组成的两亲性聚合物，纳米粒子可以在低临界胶束浓度下自组装。核磁共振氢谱（HNMR）和透射电子显微镜结果表明，纳米粒子中的响应性二硫键在还原环境中被特异性裂解，导致芘残基原位自聚集，紫外光谱和荧光光谱结果证实了这一点。此外，共聚焦激光显微镜和流式细胞术表明，与不敏感组相比，在紫外线照射下暴露于纳米粒子的癌细胞中ROS水平上调，导致细胞凋亡。因此，该策略为癌症治疗开辟了一种新方法。
