Biodegradable nanoplatform upregulates tumor microenvironment acidity for enhanced cancer therapy via synergistic induction of apoptosis, ferroptosis, and anti-angiogenesis

Journal of Nanobiotechnology

Research

Li Zhang¹  Yu Sun²  Xiaodan Huang³  Lang Ran³  Caiyun Zhang³  Peng Wang³  Ya’ nan Zhang³  Wenjuan Gao³  Pengpeng Lu³  Yinfeng Wang³  Huan Xin⁴  Xiaotong Xu⁴  Guilong Zhang⁴ 

[1] Department of Urology, the First Affiliated Hospital of Anhui Medical University, Institute of Urology, Anhui Medical University and Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, 230022, Hefei, Anhui, People’s Republic of China;Institute of Aging Medicine, Binzhou Medical University, 264003, Yantai, Shandong, China;Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences, University of Chinese Academy of Sciences, 200031, Shanghai, China;Department of Medicine and VAPSHCS, University of Washington, 98195, Seattle, WA, USA;School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, 264003, Yantai, People’s Republic of China;School of Pharmacy, Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis and Treatment, Binzhou Medical University, 264003, Yantai, People’s Republic of China;Institute of Aging Medicine, Binzhou Medical University, 264003, Yantai, Shandong, China;

关键词: Biodegradable nanoplatform;    Tumor microenvironment;    Increased acidity;    Starvation therapy;    Enhanced chemodynamic therapy;   

DOI  :  10.1186/s12951-023-01814-5

 received in 2022-12-25, accepted in 2023-02-14,  发布年份 2023

来源: Springer

【 摘 要 】

Chemodynamic therapy of cancer is limited by insufficient endogenous H2O2 generation and acidity in the tumor microenvironment (TME). Herein, we developed a biodegradable theranostic platform (pLMOFePt-TGO) involving composite of dendritic organosilica and FePt alloy, loaded with tamoxifen (TAM) and glucose oxidase (GOx), and encapsulated by platelet-derived growth factor-B (PDGFB)-labeled liposomes, that effectively uses the synergy among chemotherapy, enhanced chemodynamic therapy (CDT), and anti-angiogenesis. The increased concentration of glutathione (GSH) present in the cancer cells induces the disintegration of pLMOFePt-TGO, releasing FePt, GOx, and TAM. The synergistic action of GOx and TAM significantly enhanced the acidity and H2O2 level in the TME by aerobiotic glucose consumption and hypoxic glycolysis pathways, respectively. The combined effect of GSH depletion, acidity enhancement, and H2O2 supplementation dramatically promotes the Fenton-catalytic behavior of FePt alloys, which, in combination with tumor starvation caused by GOx and TAM-mediated chemotherapy, significantly increases the anticancer efficacy of this treatment. In addition, T2-shortening caused by FePt alloys released in TME significantly enhances contrast in the MRI signal of tumor, enabling a more accurate diagnosis. Results of in vitro and in vivo experiments suggest that pLMOFePt-TGO can effectively suppress tumor growth and angiogenesis, thus providing an exciting potential strategy for developing satisfactory tumor theranostics.

【 授权许可】

CC BY   
© The Author(s) 2023

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