KTH Royal Institute of Technology, Department of Fiber and Polymer Technology, Teknikringen 56-58, Stockholm, SE-100 44, Sweden.
Xi'an Jiaotong University, School of Mechanical Engineering, Institute of Design Science and Basic Components, Xi'an, 710049, P. R. China.
Small. 2021 Apr;17(17):e2007305. doi: 10.1002/smll.202007305. Epub 2021 Mar 16.
Multi-drug delivery systems constructed from a basic polymeric scaffold, and which have the ability to target a variety of biomedical applications, can streamline the development of nanomedicine to provide both environmental and economical relief. Herein, amphiphilic ABA-triblock copolymers are synthesized and assembled sequentially into micelles and nanogels as drug delivery systems following a thorough evaluation on advanced in vitro models to explore their potential for the treatment of cancer and bacterial infections. Short blocks of 5-methyl-5-allyloxycarbonyl-1,3-dioxan-2-one (MAC) are oligomerized from PEG6k and thereafter functionalized with dihydroxyphenylalanine (dopa)-functional thiols using thiol-ene coupling (TEC) click chemistry. The copolymers self-assemble into well-defined micelles in aqueous solution and are further formulated into nanogels via UV-induced TEC. The resulting spherical micelles and nanogels are stable nanoparticles, with sizes ranging between 100 and 200 nm. The nanogels are found to be non-toxic to a panel of cell lines and mask the toxicity of the potent drugs until their release. The nanogels would be superior to micelles for the elimination of cancer cells supported by both 2D cell culture and a 3D spheroid model. The opposite conclusion could be drawn for bacteria inhibition.
由基本聚合物支架构建的多药物递送系统，并且具有靶向多种生物医学应用的能力，可以简化纳米医学的发展，为环境和经济提供缓解。在此，合成了两亲性 ABA 三嵌段共聚物，并在先进的体外模型上进行了彻底评估，以探索其在癌症和细菌感染治疗中的潜力，随后将其顺序组装成胶束和纳米凝胶作为药物递送系统。短链的 5-甲基-5-烯丙氧羰基-1,3-二氧戊环-2-酮 (MAC) 从 PEG6k 低聚化，然后使用硫醇-烯点击化学 (TEC) 将二羟基苯丙氨酸 (dopa)-功能化硫醇功能化。共聚物在水溶液中自组装成具有良好定义的胶束，并通过 UV 诱导的 TEC 进一步配制为纳米凝胶。所得的球形胶束和纳米凝胶是稳定的纳米颗粒，粒径在 100-200nm 之间。纳米凝胶对一系列细胞系无毒性，并掩盖了有效药物的毒性，直到其释放。纳米凝胶在消除癌细胞方面优于胶束，这一结论得到了二维细胞培养和三维球体模型的支持。对于抑制细菌，得到的结论正好相反。
