College of Chemistry and Chemical Engineering, Yantai University, Yantai 264005, China.
Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH 43210, United States.
Curr Med Chem. 2019;26(13):2377-2388. doi: 10.2174/0929867324666170830102409.
Stimuli-responsive carriers are a class of drug delivery systems which can change their physicochemical properties and/or structural conformations in response to specific stimuli. Although passive and active drug targeting has proved to reduce the side effects to normal cells, controlled intracellular drug release should be included in drug carriers to enhance the bioavailability of drugs at the disease site.
This review focuses on several recent advances in the development of stimuli-responsive carriers for spatially and temporally controlled release of therapeutic agents in response to intracellular stimuli, such as pH, redox potential, reactive oxygen species, enzyme and temperature.
Among the different types of stimuli, pH-responsive carriers have been mostly used to design intracellular controlled release system. The sharp difference of redox potential between inside and outside cells is attributed to the high variation in concentration of glutathione. ROS-responsive carriers are gaining much attention for selective release of therapeutic agents by sensing oxidative conditions at different levels. The advantages of utilizing enzymes as the trigger of stimuli-responsive carriers include diverse types of enzymes, high selectivity of enzyme catalyzed reactions and the mild reaction conditions involved. Abnormal temperature is another unique stimulus and has been widely used to trigger controlled release of drug in tumor cells.
Recent developments highlighted in this paper demonstrate that stimuli-responsive carriers possess great potential as a new platform for controlled intracellular drug release.
刺激响应载体是一类药物输送系统，其可以响应特定刺激改变其物理化学性质和/或结构构象。虽然被动和主动药物靶向已被证明可以减少对正常细胞的副作用，但应该在药物载体中包含控制细胞内药物释放，以提高药物在疾病部位的生物利用度。
本综述重点介绍了几种最近在开发刺激响应载体方面的进展，这些载体可以响应细胞内刺激（如 pH、氧化还原电位、活性氧物种、酶和温度）实现治疗剂的时空控制释放。
在不同类型的刺激中，pH 响应载体已被广泛用于设计细胞内控制释放系统。细胞内外氧化还原电位的巨大差异归因于谷胱甘肽浓度的高度变化。ROS 响应载体由于可以通过感应不同水平的氧化条件来选择性释放治疗剂，因此受到越来越多的关注。利用酶作为刺激响应载体的触发剂的优点包括酶的种类繁多、酶催化反应的高选择性以及所涉及的温和反应条件。异常温度是另一种独特的刺激因素，已被广泛用于触发肿瘤细胞中药物的控制释放。
本文强调的最新发展表明，刺激响应载体作为控制细胞内药物释放的新平台具有巨大潜力。
