期刊
CHEMICAL ENGINEERING JOURNAL
卷 446, 期 -, 页码 -出版社
ELSEVIER SCIENCE SA
DOI: 10.1016/j.cej.2022.136929
关键词
Osteosarcoma; PARP inhibitor; NIR-II fluorescence imaging; Photodynamic therapy; Chemotherapy; DNA damage
资金
- National Key R&D Program of China, China [2020YFA0908800]
- National Natural Science Foundation of China (NFSC), China [82111530209, 81773674, 81573383, 91959103, 81870162, 21763002]
- Applied Basic Research Program of Wuhan Municipal Bureau of Science and Technology, China [2019020701011429]
- Shenzhen Science and Technology Research Grant, China [JCYJ20190808152019182]
- Hubei Province Scientific and Technical Innovation Key Project, China [2020BAB058]
- Local Development Funds of Science and Technology Department of Tibet, China [XZ202001YD0028C, XZ202102YD0033C]
This study evaluates a unique strategy using a NIR-II fluorescent photosensitizer in combination with a DDR inhibitor to improve the therapeutic efficacy of osteosarcoma treatment. The results demonstrate that this strategy significantly enhances anti-tumor effects and has good bioavailability with low toxicity.
DNA damage response (DDR) inhibitors potentiate the therapeutic efficacy in osteosarcoma (OS) treatment. However, drug resistance, severe collateral toxicity, and poor bioavailability of DDR inhibitors in vivo are the main challenges. The NIR-II fluorescence image-guided photodynamic therapy exhibits advantageous properties and shows great potential in oncology, representing an emerging class of non-invasive treatment methods. Herein, a unique, synergistic strategy is evaluated to improve the therapeutic efficacy of a DDR inhibitor (AZD2461) and a diketopyrrolopyrrole-based NIR-II fluorescent photosensitizer DT. The novel NIR-II photosensitizer DT is synthesized based on diacyl-substituted diketopyrrolopyrrole, and co-encapsulated with AZD-2461 using DSPE-mPEG5000-FA to form DTA dots. DTA dots significantly enhanced anti-osteosarcoma effects by increasing the generation of reactive oxygen species (ROS) and inhibiting DNA damage repair. NIR-II image-guided synergistic enhancement with high spatiotemporal resolution and strong tumor uptake is demonstrated in vivo, resulting in improved tumor control and increased apoptosis. This work reports for the first time a novel NIR-II phototheranostic nanoplatform for OS combination therapy without severe side effects, providing a practical strategy for simultaneous cancer diagnostics, therapeutics, and postoperative real-time monitoring.
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