School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, China.
Tianjin Academy of Traditional Chinese Medicine Affiliated Hospital, Tianjin 300120, China.
J Control Release. 2022 May;345:475-493. doi: 10.1016/j.jconrel.2022.03.041. Epub 2022 Mar 23.
Azobenzene-based molecules show unique trans-cis isomerization upon ultraviolet light irradiation, which induce the change of polarity, crystallinity, stability, and binding affinity with pharmacological target. Moreover, azobenzene is the substrate of azoreductase that is often overexpressed in many pathological sites, e.g. hypoxic solid tumor. Therefore, azobenzene can be a multifunctional molecule in material science, pharmaceutical science and biomedicine because of its sensitivity to light, hypoxia and certain enzymes, hence showing potential application in site-specific smart therapy. Herein we focus on the employment of azobenzene and its derivatives for engineering triggered prodrugs and drug delivery systems, and provide an overview of photoswitchable azo-based prodrugs, the associated problems regarding the reversible isomerization and tissue penetration of ultraviolet (UV) light, as well as the potential solutions. We also present the advance of azo-bearing delivery vehicles wherein azobenzene acts as the linker, capping agent, and building block, and discuss the corresponding mechanisms for controlled cargo release, endocytosis enhancement and sensitization of free radical cancer therapy.
偶氮苯类分子在紫外光照射下表现出独特的顺反异构化，这导致其极性、结晶度、稳定性和与药理学靶标的结合亲和力发生变化。此外，偶氮苯是偶氮还原酶的底物，这种酶在许多病理部位（如缺氧的实体瘤）中常常过度表达。因此，偶氮苯由于对光、缺氧和某些酶的敏感性，可以成为材料科学、药物科学和生物医学中的多功能分子，从而在特定部位的智能治疗中显示出潜在的应用。本文主要关注偶氮苯及其衍生物在工程触发前药和药物传递系统中的应用，并提供光致变色偶氮前药的概述，包括与可逆异构化和紫外线（UV）光组织穿透相关的问题，以及潜在的解决方案。我们还介绍了含偶氮的载体的进展，其中偶氮苯作为连接子、封端剂和构建块，讨论了控制货物释放、内吞作用增强和自由基癌症治疗敏化的相应机制。
