Laser-activatable oxygen self-supplying nanoplatform for efficiently overcoming colorectal cancer resistance by enhanced ferroptosis and alleviated hypoxic microenvironment

Biomaterials Research

Research Article

Edouard C. Nice¹  Shaojiang Zheng²  Zhihan Wang³  Bowen Li³  Hailong Tian³  Wei Zhang³  Kangjia Luo⁴  Yuping Zhou⁴  Feng Gao⁴  Shuaijun Lu⁴  Rui Chen⁴  Hao Jiang⁴  Canhua Huang⁵ 

[1] Department of Biochemistry and Molecular Biology, Monash University, 3800, Clayton, VIC, Australia;Hainan Cancer Center and Tumor Institute, The First Affiliated Hospital of Hainan Medical University, 570102, Haikou, China;State Key Laboratory of Biotherapy and Cancer Center, West China School of Basic Medical Sciences & Forensic Medicine, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;The First Hospital of Ningbo University, 315020, Ningbo, China;The First Hospital of Ningbo University, 315020, Ningbo, China;State Key Laboratory of Biotherapy and Cancer Center, West China School of Basic Medical Sciences & Forensic Medicine, Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, 610041, Chengdu, China;

关键词: Colorectal cancer;    Chemo-resistance;    Ferroptosis;    Chemo-photothermal therapy;    Hypoxia;   

DOI  :  10.1186/s40824-023-00427-1

 received in 2023-07-05, accepted in 2023-08-30,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundColorectal cancer (CRC) is the second most deadly cancer worldwide, with chemo-resistance remaining a major obstacle in CRC treatment. Notably, the imbalance of redox homeostasis-mediated ferroptosis and the modulation of hypoxic tumor microenvironment are regarded as new entry points for overcoming the chemo-resistance of CRC.MethodsInspired by this, we rationally designed a light-activatable oxygen self-supplying chemo-photothermal nanoplatform by co-assembling cisplatin (CDDP) and linoleic acid (LA)-tailored IR820 via enhanced ferroptosis against colorectal cancer chemo-resistance. In this nanoplatform, CDDP can produce hydrogen peroxide in CRC cells through a series of enzymatic reactions and subsequently release oxygen under laser-triggered photothermal to alleviate hypoxia. Additionally, the introduced LA can add exogenous unsaturated fatty acids into CRC cells, triggering ferroptosis via oxidative stress-related peroxidized lipid accumulation. Meanwhile, photothermal can efficiently boost the rate of enzymatic response and local blood flow, hence increasing the oxygen supply and oxidizing LA for enhanced ferroptosis.ResultsThis nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models.ConclusionsTaken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance.Graphical Abstract

【 授权许可】

CC BY   
© The Korean Society for Biomaterials 2023

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