Jazani Arman Moini, Arezi Newsha, Maruya-Li Keaton, Jung Sungmin, Oh Jung Kwon
Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke St. W., Montreal, Quebec, Canada H4B 1R6.
ACS Omega. 2018 Aug 13;3(8):8980-8991. doi: 10.1021/acsomega.8b01310. eCollection 2018 Aug 31.
We report new dual acidic pH/reduction-responsive degradable amphiphilic block copolymers featured with dual acidic pH-labile acetal linkage and a reductively-cleavable disulfide bond at the hydrophilic/hydrophobic block junction as well as pendant disulfide bonds in the hydrophobic block. Centered on the use of a macroinitiator approach, three strategies utilize the combination of atom transfer radical polymerization and reversible addition fragmentation chain transfer polymerization in a sequential or concurrent mechanism, along with facile coupling reactions. Combined structural analysis with dual-stimuli-responsive degradation investigation allows better understanding of the architectures and orthogonalities of the formed block copolymers as a diblock or a triblock copolymer. Our study presents the development of effective synthetic strategies to well-defined multifunctional amphiphilic block copolymers that exhibit dual-stimuli-responsive degradation at dual location (called the DL-DSRD strategy), thus potentially promising as nanoassemblies for effective drug delivery.
我们报道了新型的双酸性pH/还原响应性可降解两亲性嵌段共聚物，其在亲水/疏水嵌段连接处具有双酸性pH不稳定缩醛键和可还原裂解的二硫键，并且在疏水嵌段中含有侧链二硫键。以大分子引发剂方法为核心，三种策略采用原子转移自由基聚合和可逆加成-断裂链转移聚合的组合，以顺序或并发机制进行，并结合了简便的偶联反应。将结构分析与双刺激响应性降解研究相结合，有助于更好地理解所形成的二嵌段或三嵌段共聚物的结构和正交性。我们的研究展示了开发有效合成策略以制备明确的多功能两亲性嵌段共聚物的过程，这些共聚物在两个位置表现出双刺激响应性降解（称为DL-DSRD策略），因此有望作为有效的药物递送纳米组装体。
