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On-line Access: 2024-08-27

Received: 2023-10-17

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Journal of Zhejiang University SCIENCE  Vol. No. P.

http://doi.org/10.1007/s42242-024-00310-5


Light/pH dual controlled drug release nanocontainer alleviates tumor hypoxia for synergistic enhanced chemotherapy, photodynamic therapy and chemodynamic therapy


Author(s):  Shihe Liu, Xin Zhang, Zhimin Bai, Yibo Yang, Jia Zhang, Kun Li, Zhiwei Liu, Ming Shi, Lixin Dong, Jidong Wang, Jian Li

Affiliation(s):  Hebei Key Laboratory of Applied Chemistry, Hebei Key Laboratory of Nanobiotechnology, Hebei Key Laboratory of Heavy Metal Deep-Remediation in Water and Resource Reuse, Yanshan University, Qinhuangdao 066004, China; more

Corresponding email(s):   Lijianbio@ysu.edu.cn

Key Words:  porous coordination network (Mn) framework, phototherapy, photodynamic therapy, chemodynamic therapy, Fenton effect


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Shihe Liu, Xin Zhang, Zhimin Bai, Yibo Yang, Jia Zhang, Kun Li, Zhiwei Liu, Ming Shi, Lixin Dong, Jidong Wang, Jian Li. Light/pH dual controlled drug release nanocontainer alleviates tumor hypoxia for synergistic enhanced chemotherapy, photodynamic therapy and chemodynamic therapy[J]. Journal of Zhejiang University Science , , (): .

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Abstract: 
photodynamic therapy (PDT) has significant advantages in treating primary tumors. However, the hypoxic tumor microenvironment hinders the generation of sufficient reactive oxygen species during PDT to effectively kill tumor cells, further greatly limiting the applications of PDT in cancer treatment. Herein, we reported a temperature/pH dual controlled drug delivery system LPC@PCN@PDA/Fe3+-AS1411 based on a porous coordination network (Mn) coated with polydopamine (PDA) and modified with an aptamer AS1411. ?-lapachone (LPC) was loaded inside the porous coordination network (Mn) framework, and Fe3+ was attached to the surface of the PDA coating. These nanoparticles (NPs) exhibited excellent multimodal cancer therapeutic effects and tumor targeting ability with their photo- and chemodynamic properties. The therapeutic effect can be enhanced by the production of sufficient oxygen by the internal hydrogen peroxide, which improves the photodynamic effect of the photosensitizer porous coordination network (Mn) and the chemotherapy effect of ?-lapachone. Notably, the conversion of Fe2+ to Fe3+ in the tumor cells exerts the fenton effect, which generates hydroxyl radicals that cause lipid peroxidation in tumor cells and induce apoptosis, thus enhancing the chemodynamic therapeutic effect. In vitro and in vivo experiments revealed that the NPs demonstrated specific tumor targeting, excellent inhibition effect on tumor growth, and biocompatibility. Together, our findings can help develop an intelligent multifunctional therapeutic nanoplatform for cancer therapy.

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