Department of Thyroid Surgery, The First Hospital of Jilin University, Changchun, Jilin, 130021, China.
State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, Jilin, 130022, China.
Angew Chem Int Ed Engl. 2020 Dec 14;59(51):23198-23205. doi: 10.1002/anie.202008732. Epub 2020 Oct 15.
The innate hypoxic microenvironment of most solid tumors has a major influence on tumor growth, invasiveness, and distant metastasis. Here, a hypoxia-activated self-immolative prodrug of paclitaxel (PTX -Azo) was synthesized and encapsulated by a peptide copolymer decorated with the photosensitizer chlorin e6 (Ce6) to prepare light-boosted PTX nanoparticle (Ce6/PTX -Azo NP). In this nanoparticle, PTX -Azo prevents premature drug leakage and realizes specific release in hypoxic tumor microenvironment and the photosensitizer Ce6 not only efficiently generates singlet oxygen under light irradiation but also acts as a positive amplifier to promote the release of PTX. The combination of photodynamic therapy (PDT) and chemotherapy results in excellent antitumor efficacy, demonstrating the great potential for synergistic cancer therapy.
大多数实体瘤的先天缺氧微环境对肿瘤的生长、侵袭和远处转移有重大影响。在这里，我们合成了一种紫杉醇（PTX-Azo）的缺氧激活自毁前体药物，并通过一种肽共聚物进行包裹，该共聚物用光敏剂氯乙酮（Ce6）进行修饰，以制备光增强的 PTX 纳米颗粒（Ce6/PTX-Azo NP）。在该纳米颗粒中，PTX-Azo 可防止药物过早泄漏，并在缺氧肿瘤微环境中实现特异性释放，而光敏剂 Ce6 不仅可在光照下高效产生单线态氧，还可作为正放大器促进 PTX 的释放。光动力疗法（PDT）和化学疗法的联合使用产生了优异的抗肿瘤疗效，显示出协同癌症治疗的巨大潜力。
