Cancer cell membrane biomimetic mesoporous silica nanotheranostics for enhanced Ferroptosis-mediated immuogenic cell death on Gastric cancer
Cancer cell membrane biomimetic mesoporous silica nanotheranostics for enhanced Ferroptosis-mediated immuogenic cell death on Gastric cancer
复制标题
DOI：
10.1016/j.cej.2022.140868
复制
发表时间：
2022-12-13
影响因子：
15.1
通讯作者：
Hu, Yanfeng
中科院分区：
文献类型：
--
作者：
Guo, Weihong;Chen, Zhian;Hu, Yanfeng
选择性诱导癌细胞的铁凋亡将是触发免疫原性细胞死亡（ICD）并随后增强免疫治疗的有前途的方法。事实上，在肿瘤部位产生毒性脂质过氧化物（LPO）和耗尽型谷胱甘肽（GSH）的效率在诱导铁凋亡中起着关键作用。本文中，通过将Mn离子掺杂的介孔二氧化硅纳米颗粒（Mn@MSN）和顺铂前药（Pt（IV））缀合，利用癌细胞膜掩蔽，构建了用于协同化学动力学和化学疗法的癌症靶向级联纳米系统（CCM@Mn@MSN-Pt（IV），CMnMPt）。由于CMnMPt的仿生表面功能化，其免疫逃逸和同源靶向行为将显著增强其肿瘤靶向和滞留能力。一旦被癌细胞内化，由于Mn@MSN的生物降解和Pt（IV）的还原，细胞内GSH将被耗尽，导致Mn 2+释放和顺铂转化（从Pt（IV）到Pt（II））。随后，生成的Pt（II））可损伤核DNA，并进一步激活烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX），从而提高下游H2 O2水平。此外，Mn 2+离子可以催化H2 O2转化为高活性的羟基自由基（中心点OH），这导致LPO含量进一步增加。总之，CMnMPt可以诱导铁凋亡介导的ICD，并招募细胞毒性T淋巴细胞，提供潜在的临床应用，以促进抗肿瘤免疫治疗。
Selective induction of ferroptosis of cancer cells would be a promising approach to trigger immunogenic cell death (ICD) and sequentially potentiate immunotherapy. Actually, the efficiency to produce toxic lipid peroxides (LPO) and deplete glutathione (GSH) at the tumor site plays a key role in inducing ferroptosis. Herein, a cancer targeted cascade nanosystem (CCM@Mn@MSN-Pt(IV), CMnMPt) was constructed for synergistic chemo-dynamic and chemotherapy by conjugating Mn ions-doped mesoporous silica nanoparticles (Mn@MSN) and cisplatin prodrug (Pt(IV)), with cancer cell membrane cloaking. Owing to the bio-mimetic surface functionali-zation, the immune escape and homologous targeting behaviors of CMnMPt would dramatically enhance its cancer targeting and retention abilities. Once internalized by cancer cells, intracellular GSH would be depleted attributed to the bio-degradation of Mn@MSN and reduced of Pt(IV), resulting in Mn2+ release and cisplatin transform (from Pt(IV) to Pt(II)). Subsequently, generated Pt(II)) could damage nuclear DNA, and further acti-vate nicotinamide adenine dinucleotide phosphate oxidases (NOXs) to enhance downstream H2O2 levels. Additionally, Mn2+ ions could catalyze H2O2 into highly reactive hydroxyl radical (center dot OH), which results in a further increase in LPO content. In summary, CMnMPt could induce ferroptosis-mediated ICD, and recruit cytotoxic T lymphocytes cells, offering potential clinical applications to facilitate anti-tumor immunotherapy.