Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke St W, Montreal, Quebec, Canada H4B 1R6.
Biomacromolecules. 2011 Oct 10;12(10):3819-25. doi: 10.1021/bm2011032. Epub 2011 Sep 14.
Novel sheddable micelles having hydrophilic coronas capable of being shed from biodegradable polylactide (PLA) cores by the cleavage of disulfide linkages in response to thiols were prepared by aqueous micellization of PLA-based amphiphilic block copolymers functionalized with disulfides at block junctions. These well-defined copolymers were synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization in the presence of a new disulfide-functionalized double-head initiator having both terminal OH and Br groups. (1)H NMR and GPC results indicate that both polymerizations were well-controlled with molecular weight distribution as low as M(w)/M(n) < 1.2. Aqueous micellization to form core/shell micelles with disulfides at the interface of PLA cores and hydrophilic coronas and their thiol-responsive degradation were investigated. In the presence of water-soluble thiols, disulfide linkages in the micelles were cleaved and hydrophilic coronas were lost, causing PLA cores to precipitate due to the loss of colloidal stability. In a biomedical perspective, the new sheddable micelles were not cytotoxic and hence biocompatible.
具有可脱落亲水冠的新型胶束，其亲水性冠能够通过二硫键的断裂从可生物降解的聚乳酸（PLA）核中脱落，这是通过在二硫键功能化的基于 PLA 的两亲嵌段共聚物的水溶液中胶束化来制备的。这些结构明确的共聚物是通过在新型二硫键功能化的双头引发剂的存在下，将开环聚合和原子转移自由基聚合结合起来合成的，该引发剂具有末端 OH 和 Br 基团。(1)H NMR 和 GPC 结果表明，两种聚合反应都得到了很好的控制，分子量分布低至 M(w)/M(n) < 1.2。研究了在水溶液中形成具有 PLA 核和亲水冠界面上二硫键的核/壳胶束的胶束化及其对硫醇的响应性降解。在水溶性硫醇的存在下，胶束中的二硫键被切断，亲水冠丢失，导致 PLA 核由于胶体稳定性的丧失而沉淀。从生物医学的角度来看，新型可脱落胶束没有细胞毒性，因此是生物相容的。
