Department of Respiration, Shanghai Public Health Clinical Center , Fudan University , Shanghai 201508 , China.
Department of Medical Materials and Rehabilitation Engineering, School of Biological and Medical Engineering , Hefei University of Technology , Hefei , Anhui 230009 , China.
ACS Appl Mater Interfaces. 2018 Jun 27;10(25):21198-21205. doi: 10.1021/acsami.8b06758. Epub 2018 Jun 13.
Nanocarrier-mediated photodynamic therapy (PDT), which involves the systemic delivery of photosensitizers (PSs) into tumor tissue and tumor cells, has emerged as an attractive treatment for cancer. However, insufficient PS release limits intracellular cytotoxic reactive oxygen species (ROS) generation, which has become a major obstacle to improving the PDT therapeutic efficacy. Herein, a novel hyperbranched polyphosphoester (hbPPE) containing numerous acetal bonds (S-hbPPE/Ce6) was explored as a chlorin e6 (Ce6) nanocarrier for PDT. S-hbPPE/Ce6 with a branched topological structure efficiently encapsulated Ce6 and then significantly enhanced its internalization by tumor cells. Subsequently, the endo-/lysosomal acid microenvironment rapidly cleaved the acetal linkage of S-hbPPE and destroyed the nanostructure of S-hbPPE/Ce6, resulting in increased Ce6 release and obviously elevated the intracellular ROS generation under illumination. Therefore, treatment with S-hbPPE/Ce6 noticeably enhanced the PDT therapeutic efficacy, indicating that such a pH-sensitive hbPPE nanocarrier has great potential to improve the PDT therapeutic efficacy for cancer therapy.
基于纳米载体的光动力疗法（PDT）将光敏剂（PSs）系统递送至肿瘤组织和肿瘤细胞中，已成为一种有吸引力的癌症治疗方法。然而，PS 的释放不足限制了细胞内细胞毒性活性氧（ROS）的产生，这已成为提高 PDT 治疗效果的主要障碍。在此，探索了一种含有大量缩醛键的新型超支化聚膦酸酯（hbPPE）（S-hbPPE/Ce6）作为氯卟啉 e6（Ce6）的 PDT 纳米载体。具有支化拓扑结构的 S-hbPPE/Ce6 可有效包裹 Ce6，然后显著增强肿瘤细胞对其的内化。随后，内体/溶酶体酸性微环境迅速切割 S-hbPPE 的缩醛键，并破坏 S-hbPPE/Ce6 的纳米结构，导致 Ce6 释放增加，并在光照下明显提高细胞内 ROS 的产生。因此，S-hbPPE/Ce6 的治疗明显增强了 PDT 的治疗效果，表明这种 pH 敏感的 hbPPE 纳米载体具有很大的潜力，可以提高癌症治疗的 PDT 治疗效果。
