State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Collaborative Innovation Center for Guangxi Ethnic Medicine, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin, 541004, PR China.
MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, School of Chemistry, Sun Yat-Sen University, Guangzhou, 510006, PR China.
Biosens Bioelectron. 2025 Jan 15;268:116906. doi: 10.1016/j.bios.2024.116906. Epub 2024 Nov 2.
Imaging guided cancer therapy is a comprehensive strategy that combines the diagnosis and treatment to eradicate tumors. Ferroptosis is a distinct programmed cell death and holds great potential in cancer therapy. In this study, a hydrogen sulfide (HS)-activated PEGylated Pd@CuO core-shell nanocomposite (termed PCO) that in situ transformed into Pd@CuS (termed PCS) at colorectal tumor tissues is developed for colorectal cancer photoacoustic (PA) imaging and photothermal-enhanced ferroptosis therapy in NIR-II window. The Cu on the surface of PCS can catalyze the Fenton-like reaction with overexpressed HO in the colon tumor tissues, yielding hydroxyl radicals (·OH) and Cu. Moreover, the PCS accelerates the Fenton-like reaction to generate more ·OH. The PCS displays dual peroxidase- and glutathione oxidase-mimic enzymatic activity in weakly acidic tumor microenvironment (TME). Additionally, the glutathione depletion by Cu results in the production of Cu and glutathione disulfide as well as the down-regulation of glutathione peroxidase 4. The interaction of polyunsaturated fatty acids with ·OH induces the up-regulation of lipid peroxides on cellular membrane, thereby causing ferroptosis. Hence, this study has developed the HS-activated PCO that in situ transforms into PCS, as a novel colon cancer diagnosis-treatment nanoprobe, for PA imaging guided precise diagnosis and efficient therapy of colon cancer.
影像引导癌症治疗是一种综合策略，将诊断和治疗结合起来以消灭肿瘤。铁死亡是一种独特的程序性细胞死亡，在癌症治疗中有很大的潜力。在这项研究中，开发了一种硫化氢 (HS) 激活的聚乙二醇化 Pd@CuO 核壳纳米复合材料（称为 PCO），它可以在结直肠肿瘤组织原位转化为 Pd@CuS（称为 PCS），用于结直肠癌光声（PA）成像和光热增强的铁死亡治疗在近红外二区（NIR-II）窗口。PCS 表面的 Cu 可以在结肠肿瘤组织中过表达的 HO 催化类芬顿反应，生成羟基自由基（·OH）和 Cu。此外，PCS 加速类芬顿反应以产生更多的·OH。PCS 在弱酸性肿瘤微环境 (TME) 中表现出双重过氧化物酶和谷胱甘肽氧化酶模拟酶活性。此外，Cu 导致谷胱甘肽耗竭，生成 Cu 和谷胱甘肽二硫化物，并下调谷胱甘肽过氧化物酶 4。多不饱和脂肪酸与·OH 的相互作用诱导细胞膜上脂质过氧化物的上调，从而导致铁死亡。因此，本研究开发了 HS 激活的 PCO，它可以原位转化为 PCS，作为一种新型的结肠癌诊断治疗纳米探针，用于 PA 成像引导的结肠癌精确诊断和有效治疗。
