Beijing National Laboratory for Molecular Sciences (BNLMS), Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, Department of Polymer Science and Engineering, College of Chemistry and Molecular Engineering , Peking University , Beijing 100871 , China.
Biomacromolecules. 2018 Jun 11;19(6):2182-2193. doi: 10.1021/acs.biomac.8b00271. Epub 2018 Apr 25.
Reactive oxygen species (ROS)-responsive polymers have attracted attention for their potential in photodynamic therapy. Herein, we report the ROS-responsive aliphatic polycarbonates prepared by the ring-opening polymerization (ROP) of three six-membered cyclic carbonate monomers with ethyl selenide, phenyl selenide or ethyl telluride groups. Under catalysis of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), all three monomers underwent the controlled anionic ROP, showing a feature of equilibrium polymerization due to the bulky effect of 5,5-disubstituents. With PEG macroinitiator, three series amphiphilic block copolymers were prepared. They could form spherical nanoparticles of ∼100 nm, which were stable in neutral phosphate buffer but dissociated rapidly under triggering of HO. We studied the HO-induced oxidation profiles of selenide- or telluride-containing small molecules by H NMR and revealed the factors that affect the oxidation kinetics and products. On this basis, the oxidative degradation mechanism of the copolymer nanoparticles has been clarified. Under the same oxidative condition, the telluride-containing nanoparticle degraded with the fastest rate while the phenyl selenide-based one degraded most slowly. These ROS-responsive nanoparticles could load photosensitizer chlorin e6 (Ce6) and anticancer drug doxorubicin (DOX). Under red light irradiation, Ce6-sensitized production of O that triggered the degradation of nanoparticles, resulting in an accelerated payload release. In vitro cytotoxicity assays demonstrate that the nanoparticles coloaded with DOX and Ce6 exhibited a synergistic cell-killing effect to MCF-7 cells, representing a novel responsive nanoplatform for PDT and/or chemotherapy.
活性氧（ROS）响应聚合物因其在光动力治疗中的潜力而受到关注。在此，我们报告了通过具有乙基硒醚、苯硒醚或乙基碲醚基团的三种六元环碳酸酯单体的开环聚合（ROP）制备的 ROS 响应脂肪族聚碳酸酯。在 1,8-二氮杂二环[5.4.0]十一-7-烯（DBU）的催化下，所有三种单体均经历了受控的阴离子 ROP，由于 5,5-双取代基的庞大效应，表现出平衡聚合的特征。使用 PEG 大分子引发剂，制备了三种系列的两亲嵌段共聚物。它们可以形成约 100nm 的球形纳米粒子，在中性磷酸盐缓冲液中稳定，但在 HO 的触发下迅速解离。我们通过 1 H NMR 研究了含硒或碲小分子的 HO 诱导氧化曲线，并揭示了影响氧化动力学和产物的因素。在此基础上，阐明了共聚物纳米粒子的氧化降解机制。在相同的氧化条件下，含碲的纳米粒子降解最快，而基于苯硒醚的纳米粒子降解最慢。这些 ROS 响应纳米粒子可以负载光敏剂氯代叶绿素 e6（Ce6）和抗癌药物阿霉素（DOX）。在红光照射下，Ce6 敏化产生的 O 触发纳米粒子的降解，导致payload 释放加速。体外细胞毒性试验表明，共载有 DOX 和 Ce6 的纳米粒子对 MCF-7 细胞表现出协同的细胞杀伤作用，代表了一种用于 PDT 和/或化疗的新型响应性纳米平台。
