School of Pharmaceutical Science & Technology, Tianjin Key Laboratory for Modern Drug Delivery & High Efficiency, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin University, Tianjin 300072, China.
Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, and Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
J Control Release. 2017 Aug 28;260:12-21. doi: 10.1016/j.jconrel.2017.05.025. Epub 2017 May 17.
Photodynamic therapy (PDT) efficacy is limited by the very short half-life and limited diffusion radius of singlet oxygen (O). We report a O-responsive micellar nanoplatform subject to considerable size-expansion upon light triggering to facilitate on-demand release of photosensitizers. Imidazole, a well-known O scavenger, was incorporated in the hydrophobic core of amphiphilic copolymer micelles, and was used to coordinate with biocompatible Zn and encapsulate the photosensitizer chlorin e6 (Ce6). The micelles are highly sensitive to light irradiation: O triggering induced dramatic particle size expansion due to the conversion of imidazole to hydrophilic urea, resulting in instantaneous release of Ce6 and rapid intracellular distribution. This O-responsive, size-expandable nanosystem delivered substantially more Ce6 to tumor sites as compared to free Ce6, and exhibited improved anti-tumor efficacy in vivo in 4T1 tumor-bearing mice. This work opens new avenues of particle expansion-induced PDT enhancement by controlled imidazole chemistry.
光动力疗法 (PDT) 的疗效受到单线态氧 (O) 半衰期极短和扩散半径有限的限制。我们报告了一种 O 响应性胶束纳米平台，在光触发下会发生显著的尺寸扩张，从而便于按需释放光敏剂。咪唑是一种众所周知的 O 清除剂，被掺入两亲性共聚物胶束的疏水核中，并用于与生物相容性 Zn 配位，封装光敏剂氯卟啉 e6 (Ce6)。胶束对光照射非常敏感：O 触发会导致咪唑转化为亲水性脲，从而导致颗粒尺寸急剧膨胀，导致 Ce6 的瞬时释放和快速细胞内分布。与游离 Ce6 相比，这种 O 响应性、可尺寸扩张的纳米系统向肿瘤部位输送了更多的 Ce6，并在 4T1 荷瘤小鼠体内表现出了更好的抗肿瘤疗效。这项工作通过控制咪唑化学为基于粒子膨胀的 PDT 增强开辟了新途径。
