结肠直肠癌（CRC）是全球第二致命的癌症，化疗抵抗仍然是CRC治疗的主要障碍。值得注意的是，氧化还原平衡介导的铁死及对缺氧肿瘤微环境的调节被视为克服CRC化疗抵抗的新切入点。受此启发，我们通过共聚组装顺铂（CDDP）和亚油酸（LA）改性的IR820，合理设计了一种光活化自供氧化学光热纳米平台，以通过增强的铁死抗击结直肠癌化疗抵抗。在这个纳米平台中，CDDP可以通过一系列酶反应在CRC细胞中产生过氧化氢，并在激光触发的光热作用下释放氧气以缓解缺氧。此外，引入的LA可以向CRC细胞中添加外源性不饱和脂肪酸，通过氧化应激相关的过氧化脂类积累触发铁死。同时，光热可以有效增加酶反应速率和局部血流，从而增加氧气供应，并氧化LA以增强铁死。这种纳米平台在化疗抵抗细胞系中表现出良好的抗肿瘤活性，并在裸小鼠异体移植模型中显示出强大的抑制能力。综上所述，这种纳米平台通过增强铁死和缓解缺氧肿瘤微环境，提供了一种有前途的范例来对抗CRC化疗抵抗。©2023年，韩国生物材料学会。

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.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.This nanoplatform exhibited excellent anti-tumor efficacy in chemo-resistant cell lines and showed potent inhibitory capability in nude mice xenograft models.Taken together, this nanoplatform provides a promising paradigm via enhanced ferroptosis and alleviated hypoxia tumor microenvironment against CRC chemo-resistance.© 2023. The Korean Society for Biomaterials.