Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment.
Reversibly crosslinked nanocarriers for on-demand drug delivery in cancer treatment.
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DOI：
10.4155/tde.12.106
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发表时间：
2012-12
影响因子：
4.2
通讯作者：
Luo J
中科院分区：
文献类型：
--
作者：
Shao Y;Huang W;Shi C;Atkinson ST;Luo J
聚合物胶束已被证明是最通用的抗癌药物递送纳米载体之一。然而，由于这些自组装系统的动态性质，胶束的体外和体内稳定性仍然是一个挑战，这导致药物过早释放和非特异性体内生物分布。最近，已经开发了可逆交联胶束以提供稳定血液循环中的纳米载体的解决方案。增加的稳定性允许纳米颗粒通过被动和/或主动肿瘤靶向有效地积聚在肿瘤部位，而胶束交联的裂解，通过内部或外部刺激，促进按需药物释放。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键的选择。然后，可逆交联胶束的发展按需药物释放响应于肿瘤微环境中的单一或双重刺激，例如，酸性pH值，还原微环境，酶微环境，光照射和竞争性试剂后胶束递送的管理进行了讨论。
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.