Frontiers Science Center for Flexible Electronics (FSCFE), Shaanxi Institute of Flexible Electronics (SIFE), and Shaanxi Institute of Biomedical Materials and Engineering (SIBME), Northwestern Polytechnical University (NPU), 127 West Youyi Road, Xi'an, Shaanxi 710072, People's Republic of China.
ACS Macro Lett. 2022 May 17;11(5):622-629. doi: 10.1021/acsmacrolett.2c00137. Epub 2022 Apr 18.
As one of the gasotransmitters, the therapeutic effects of hydrogen sulfide (HS) were reported widespread in recent years. Considering the short physiological half-life and significant dose-dependent effects of HS, it is vital to achieve controlled HS delivery for biomedical applications. Polymeric micelles have been explored to regulate HS delivery. However, the dilution-induced dissociation of micelles in physiological conditions limits their therapeutic effects. The circulation stability of polymeric micelles could be improved through core-cross-linking, but reduced HS releasing efficiency is usually unavoidable. To solve these problems, we developed di--substituted -aroylthiooximes (-diSATOs) as linkers, which integrated cross-linking of micelle core and conjugation of HS donors through one simple reaction. Compared with SATO-bearing non-cross-linked micelle, the core-cross-linked micelle (CCM) prepared through this method exhibited initial rapid HS release owing to the electron-withdrawing effect of -diSATOs, and subsequently, a sustained release could last for a long period of time. Considering the characteristic HS releasing behavior of CCM, it may accelerate wound healing through initial efficient and subsequent prolonged pro-healing effects. As a proof of concept, we explored the therapeutic potential of CCM using a murine burn wound model, which exhibited pro-healing effect on burn wounds.
作为一种气体递质,近年来硫化氢(HS)的治疗效果被广泛报道。鉴于 HS 的生理半衰期短且剂量依赖性显著,实现对其的控制释放对于生物医学应用至关重要。聚合物胶束已被探索用于调节 HS 的释放。然而,在生理条件下胶束的稀释诱导解离限制了其治疗效果。通过核交联可以提高聚合物胶束的循环稳定性,但通常不可避免地会降低 HS 的释放效率。为了解决这些问题,我们开发了二取代的芳酰硫肟(-diSATOs)作为连接体,通过一个简单的反应将胶束核交联和 HS 供体偶联集成在一起。与含有 SATO 的非交联胶束相比,通过这种方法制备的核交联胶束(CCM)由于 -diSATOs 的吸电子效应,初始时迅速释放 HS,随后可以持续释放很长一段时间。鉴于 CCM 的 HS 释放特性,它可能通过初始的高效和随后的延长的促愈合作用来加速伤口愈合。作为概念验证,我们使用小鼠烧伤模型探索了 CCM 的治疗潜力,该模型对烧伤伤口表现出促愈合作用。