期刊
CHEMICAL SCIENCE
卷 12, 期 35, 页码 11810-11820出版社
ROYAL SOC CHEMISTRY
DOI: 10.1039/d1sc01888d
关键词
-
资金
- Jiangsu Province Hi-tech Key Laboratory for Biomedical Research
A hypoxia-activated bifunctional prodrug was designed and encapsulated by a photo-responsive polymer to create a light-controlled multi-step drug release system for tumor hypoxia therapy. In vivo studies demonstrated that the prodrug exhibited high efficiency in tumor regression through the synergistic effect of photodynamic therapy and hypoxia-activated chemotherapy.
Hypoxia is a major obstacle for cancer therapy due to its association with cell proliferation, tumor distant metastasis, and treatment resistance. In this study, a hypoxia-activated bifunctional prodrug (CC5) was designed, synthesized and encapsulated by a photo-responsive ruthenium complex-derived polymer to yield a light-controlled multi-step drug release system (CC5-RuCa) for synergistic therapy against tumor hypoxia. Under NIR irradiation, CC5-RuCa not only generated ROS to kill the cancer cells in the exterior of the tumor but also released the prodrug CC5 with enhanced intratumoral penetration in the severe hypoxia region inside the tumor tissue. In vivo studies on MDA-MB-231 xenograft models revealed that CC5-RuCa with preferential accumulation in the tumor exhibited highly efficient tumor regression through the synergistic effect of photodynamic therapy and hypoxia-activated chemotherapy.
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