Author:
Jiang Hao,Tian Hailong,Wang Zhihan,Li Bowen,Chen Rui,Luo Kangjia,Lu Shuaijun,Nice Edouard C.,Zhang Wei,Huang Canhua,Zhou Yuping,Zheng Shaojiang,Gao Feng
Abstract
Abstract
Background
Colorectal 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.
Methods
Inspired 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.
Results
This nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models.
Conclusions
Taken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance.
Graphical Abstract
Funder
Natural Science Foundation of Ningbo
West China Hospital, Sichuan University
Publisher
American Association for the Advancement of Science (AAAS)
Subject
Biomedical Engineering,Biomaterials,Medicine (miscellaneous),Ceramics and Composites
Reference56 articles.
1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and Mortality Worldwide for 36 cancers in 185 countries. Cancer J Clin. 2021;71:209–49.
2. Kataoka Y, Ohshio Y, Teramoto K, Igarashi T, Asai T, Hanaoka J. Hypoxia–induced galectin–3 enhances RhoA function to activate the motility of tumor cells in non–small cell lung cancer. Oncol Rep. 2019;41:853–62.
3. Song D, Beringhs AO, Zhuang Z, Joshi G, Tran TH, Claffey KP, Yuan H, Lu X. Overcoming hypoxia-induced chemoresistance to cisplatin through tumor oxygenation monitored by optical imaging. Nanotheranostics. 2019;3:223–35.
4. Perillo B, Di Donato M, Pezone A, Di Zazzo E, Giovannelli P, Galasso G, Castoria G, Migliaccio A. ROS in cancer therapy: the bright side of the moon. Exp Mol Med. 2020;52:192–203.
5. Kang N, Son S, Min S, Hong H, Kim C, An J, Kim JS, Kang H. Stimuli-responsive ferroptosis for cancer therapy. Chem Soc Rev. 2023;52:3955–72.
Cited by
4 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献