Department of Chemical and Biomolecular Engineering, National University of Singapore, 4 Engineering Drive 4, Singapore 117585, Singapore.
Key Laboratory of Cluster Science, Ministry of Education, School of Chemistry and Chemical Engineering, Beijing Institute of Technology, 5 South Zhongguancun Street, Beijing 100081, China.
ACS Nano. 2020 Oct 27;14(10):13056-13068. doi: 10.1021/acsnano.0c04518. Epub 2020 Oct 5.
Tumor accumulation and intratumoral singlet oxygen (O) generation efficiency of photosensitizers (PSs) are two essential factors that determine their photodynamic therapy (PDT) efficacies. How to maximize the PS performance at the tumor site is of great research interest. Herein, we report a metal-organic framework (ZIF-8, ZIF = zeolitic imidazolate framework) assisted self-assembly nanoplatform, ZIF-8-PMMA-S-S-mPEG, as an effective tool for organic PS payloads to achieve efficient PDT. Using an organic PS with aggregation-induced emission as an example, under intratumoral bioreduction, PS-loaded ZIF-8-PMMA-S-S-mPEG (PS@ZIF-8-PMMA-S-S-mPEG) was self-assembled into large ordered hydrophobic clusters, which greatly enhance tumor retention and accumulation of the PS. Moreover, hydrophobic ZIF-8 assemblies greatly isolate the loaded PSs from water and improve O transport for the PSs to effectively produce O inside tumors under light irradiation. The organic PS is therefore endowed with optimal tumor accumulation and intratumoral O production, demonstrating the effectiveness of the developed self-assembly strategy in PDT application.
肿瘤积累和光敏剂（PS）的肿瘤内单线态氧（O）生成效率是决定其光动力疗法（PDT）疗效的两个重要因素。如何最大限度地提高肿瘤部位的 PS 性能是一个非常有研究意义的问题。在此，我们报告了一种金属有机骨架（ZIF-8，ZIF = 沸石咪唑骨架）辅助的自组装纳米平台，ZIF-8-PMMA-S-S-mPEG，作为一种有效的工具，用于有机 PS 有效负载物以实现有效的 PDT。使用具有聚集诱导发射的有机 PS 作为示例，在肿瘤内生物还原下，负载 PS 的 ZIF-8-PMMA-S-S-mPEG（PS@ZIF-8-PMMA-S-S-mPEG）自组装成大的有序疏水性簇，这极大地增强了 PS 在肿瘤中的保留和积累。此外，疏水性 ZIF-8 组装体将负载的 PS 与水隔离开来，并改善 O 向 PS 的传输，以使 PS 在光照射下有效地在肿瘤内产生 O。因此，该有机 PS 具有最佳的肿瘤积累和肿瘤内 O 生成，证明了所开发的自组装策略在 PDT 应用中的有效性。
