Maruya-Li Keaton, Shetty Chaitra, Moini Jazani Arman, Arezi Newsha, Oh Jung Kwon
Department of Chemistry and Biochemistry, Concordia University, Montreal, Quebec H4B 1R6, Canada.
ACS Omega. 2020 Feb 12;5(7):3734-3742. doi: 10.1021/acsomega.9b04430. eCollection 2020 Feb 25.
We report a thermoresponsive double hydrophilic block copolymer degradable in response to dual reduction and acidic pH at dual locations. The copolymer consists of a poly(ethylene oxide) block covalently connected through an acid-labile acetal linkage with a thermoresponsive polymethacrylate block containing pendant oligo(ethylene oxide) and disulfide groups. The copolymer undergoes temperature-driven self-assembly in water to form nanoassemblies with acetal linkages at the core/corona interface and disulfide pendants in the core, exhibiting dual reduction/acid responses at dual locations. The physically assembled nanoaggregates are converted to disulfide-core-crosslinked nanogels through disulfide-thiol exchange reaction, retaining enhanced colloidal stability, yet degraded to water-soluble unimers upon reduction/acid-responsive degradation. Further, the copolymer exhibits improved tunability of thermoresponsive property upon the cleavage of junction acetal and pendant disulfide linkages individually and in combined manner. This work suggests that dual location dual reduction/acid-responsive degradation is a versatile strategy toward effective drug delivery exhibiting disulfide-core-crosslinking capability and disassembly as well as improved thermoresponsive tunability.
我们报道了一种热响应性双亲水嵌段共聚物，其可在两个位置响应双重还原和酸性pH而降解。该共聚物由一个聚环氧乙烷嵌段组成，该嵌段通过酸不稳定的缩醛键与一个含有侧链低聚环氧乙烷和二硫键的热响应性聚甲基丙烯酸酯嵌段共价连接。该共聚物在水中经历温度驱动的自组装，形成纳米组装体，在核/冠界面处有缩醛键，在核中有二硫键侧链，在两个位置表现出双重还原/酸响应。通过二硫键-硫醇交换反应，物理组装的纳米聚集体转化为二硫键核心交联的纳米凝胶，保持增强的胶体稳定性，但在还原/酸响应降解后降解为水溶性单聚物。此外，该共聚物在连接缩醛和侧链二硫键单独或联合断裂时，热响应性能的可调性得到改善。这项工作表明，双位置双重还原/酸响应降解是一种通用策略，可用于实现具有二硫键核心交联能力、可拆解以及改善热响应可调性的有效药物递送。
