Zinc oxide nanosphere for hydrogen sulfide scavenging and ferroptosis of colorectal cancer

Journal of Nanobiotechnology

Sheng Yao¹  Wei Lu²  Kefeng Ding³  Xiang Pan³  Min Zhou⁴  Jian He⁵  Yuchen Qi⁵  Zhen Du⁶ 

[1] Cancer Center, Zhejiang University, 310058, Hangzhou, China;Laboratory of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310029, Hangzhou, China;Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China;Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China;Cancer Center, Zhejiang University, 310058, Hangzhou, China;Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, 310009, Hangzhou, China;Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China;State Key Laboratory of Modern Optical Instrumentations, Zhejiang University, 310058, Hangzhou, China;Cancer Center, Zhejiang University, 310058, Hangzhou, China;Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China;Institute of Translational Medicine, Zhejiang University, 310029, Hangzhou, China;The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, 310022, Hangzhou, Zhejiang, China;

关键词: Zinc oxide nanoparticles;    Hydrogen sulfide;    Colorectal cancer;    Ferroptosis;    Nanoengineering;    Glutathione;   

DOI  :  10.1186/s12951-021-01069-y

来源: Springer

【 摘 要 】

BackgroundColorectal cancer is a common malignancy occurring in the digestive system and ranks second in cancer mortality worldwide. In colorectal cancer, hydrogen sulfide (H2S) is selectively upregulated, resulting in the further exacerbation of the disease. Therefore, the clearance of H2S and the regulation of the enzymes on the H2S pathways are of great significance for colorectal cancer therapy.MethodsHere, we investigated the H2S content in various clinical tumor tissues from patients and confirmed that overproduced concentration of H2S in colorectal cancer. Accordingly, we developed an H2S-responsive nanoplatform based on zinc oxide coated virus-like silica nanoparticles (VZnO) for the therapy of colorectal cancer.ResultsOwing to its excellent H2S scavenging ability, VZnO could effectively reduce H2S content in colorectal cancer to prohibit the growth of CT26 and HCT116 colorectal cancer cells. Moreover, the removal of H2S in colorectal cancer also leads to tumor inhibition through activating ferroptosis, a non-apoptotic form of cell death. The biosafety-related toxicological and pathological analysis confirmed the low toxicity and high safety of VZnO in colorectal cancer treatment. Furthermore, as an H2S-responsible nanosystem, VZnO appears to have no therapeutic effect on other non H2S rich cancers, such as the 4T1 breast cancer model.ConclusionsWe anticipate that the H2S-depletion-induced ferroptosis strategy using zinc oxide-based nanomaterials would provide insights in designing nanomedicines for colorectal cancer-target theranostics and may offer clinical promise.Graphic abstract

【 授权许可】

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