Shao Yu, Huang Wenzhe, Shi Changying, Atkinson Sean T, Luo Juntao
Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
Ther Deliv. 2012 Dec;3(12):1409-27. doi: 10.4155/tde.12.106.
Polymer micelles have proven to be one of the most versatile nanocarriers for anticancer drug delivery. However, the in vitro and in vivo stability of micelles remains a challenge due to the dynamic nature of these self-assembled systems, which leads to premature drug release and nonspecific biodistribution in vivo. Recently, reversibly crosslinked micelles have been developed to provide solutions to stabilize nanocarriers in blood circulation. Increased stability allows nanoparticles to accumulate at tumor sites efficiently via passive and/or active tumor targeting, while cleavage of the micelle crosslinkages, through internal or external stimuli, facilitates on-demand drug release. In this review, various crosslinking chemistries as well as the choices for reversible linkages in these nanocarriers will be introduced. Then, the development of reversibly crosslinked micelles for on-demand drug release in response to single or dual stimuli in the tumor microenvironment is discussed, for example, acidic pH, reducing microenvironment, enzymatic microenvironment, photoirradiation and the administration of competitive reagents postmicelle delivery.
聚合物胶束已被证明是用于抗癌药物递送的最通用的纳米载体之一。然而,由于这些自组装系统的动态性质,胶束在体外和体内的稳定性仍然是一个挑战,这会导致药物过早释放和体内非特异性生物分布。最近,可逆交联胶束已被开发出来,以解决在血液循环中稳定纳米载体的问题。稳定性的提高使纳米颗粒能够通过被动和/或主动肿瘤靶向有效地在肿瘤部位积累,而通过内部或外部刺激裂解胶束交联则有助于按需释放药物。在这篇综述中,将介绍各种交联化学以及这些纳米载体中可逆连接的选择。然后,讨论了用于响应肿瘤微环境中的单一或双重刺激(例如酸性pH、还原微环境、酶促微环境、光照射以及胶束递送后竞争性试剂的给药)而按需释放药物的可逆交联胶束的发展。
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