Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China; Department of Polymeric Materials, School of Materials Science and Engineering, Tongji University, 4800 Caoan Road, Shanghai 201804, China.
Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China.
J Control Release. 2020 Jun 10;322:81-94. doi: 10.1016/j.jconrel.2020.03.013. Epub 2020 Mar 13.
Stimuli-responsive anticancer drug delivery vehicles have attracted increasing attention in nanomedicine. However, controlled drug release in vivo is still an important challenge, as traditional stimuli lack maneuverability. To solve this problem, we designed an ultrasound and pH-responsive polymersome by self-assembly of poly(ethylene oxide)-block-poly(2-(diethylamino)ethyl methacrylate)-stat-poly(methoxyethyl methacrylate) [PEO-b-P(DEA-stat-MEMA)], where PEO acts as the corona-forming block, DEA acts as the endosomal escape segment, and MEMA acts as the ultrasound-responsive segment. This strategy combines the advantages of noninvasive ultrasonic stimulus which can be applied from outside to any organ regardless of depth, and the weakly acidic microenvironment of tumor tissue. In vitro experiments confirmed excellent endosomal escape ability, on-demand drug release behavior, low cytotoxicity, and high intracellular delivery efficiency of polymersomes. In vivo antitumor tests revealed that in the presence of sonication, the anticancer drug was released at an accelerated rate from these ultrasound-responsive polymersomes, and the DOX-loaded polymersomes + sonication group significantly inhibited tumor growth (95% reduction in tumor mass) without any side effects. Overall, this ultrasound-responsive polymersome provides us with a fresh insight into designing next-generation stimuli-responsive drug carriers with better maneuverability and higher chemotherapeutic efficiency.
刺激响应型抗癌药物递送载体在纳米医学中受到了越来越多的关注。然而，体内的药物控制释放仍然是一个重要的挑战，因为传统的刺激源缺乏可操作性。为了解决这个问题，我们通过聚（乙二醇）-嵌段-聚（2-（二乙氨基）乙基甲基丙烯酸酯）-嵌段-聚（甲氧基乙基甲基丙烯酸酯）[PEO-b-P（DEA-stat-MEMA）]的自组装设计了一种超声和 pH 响应聚合物囊泡，其中 PEO 作为冠形成嵌段，DEA 作为内涵体逃逸段，MEMA 作为超声响应段。该策略结合了非侵入性超声刺激的优势，这种刺激可以从外部应用于任何器官，无论深度如何，并且可以利用肿瘤组织的弱酸性微环境。体外实验证实了聚合物囊泡具有优异的内涵体逃逸能力、按需药物释放行为、低细胞毒性和高细胞内递送效率。体内抗肿瘤试验表明，在超声刺激下，这些超声响应聚合物囊泡中的抗癌药物以更快的速度释放，载 DOX 的聚合物囊泡+超声组显著抑制了肿瘤生长（肿瘤质量减少 95%），没有任何副作用。总的来说，这种超声响应聚合物囊泡为我们设计具有更好的可操作性和更高化疗效率的下一代刺激响应型药物载体提供了新的思路。
