纳米级含卟啉共价有机聚合物通过谷胱甘肽消耗增强肿瘤细胞光动力治疗中的铁死亡。
Nanosized Porphyrin-Containing Covalent Organic Polymer to Enhance Ferroptosis in Photodynamic Treatment of Tumor Cells via Glutathione Depletion.
发表日期：2024 Aug 30
作者：
Jiahao Zhang, Anna Zhang, Siyu Liu, Zhipeng Dong, Junkai Zhao, Yufeng Sun, Qiuxian Wei, Dan Wang, Saifei Wang, Anping Yu, Zhong Rui Li, Ran Yan, Yue Wang
来源：
BIOCONJUGATE CHEMISTRY
摘要：
由5,10,15,20-四(4-羧基苯基)卟啉(TCPP)和胱胺通过酰化反应制备了含卟啉的纳米级共价有机聚合物(COP)。一方面，TCPP可以通过激光照射诱导肿瘤细胞死亡。由于胱胺中存在二硫键，可与谷胱甘肽发生反应，导致肿瘤细胞中谷胱甘肽的消耗和过氧化物的积累。最终通过透明质酸封装COP得到S-COP@HA，尺寸为168.6 nm的纳米粒子也表现出良好的肿瘤蓄积性和生物安全性。在相对较低的激光密度下连续两次施用 S-COP@HA 后，观察到肿瘤细胞生长的显着抑制。这种联合疗法被证明可以降低肿瘤细胞中还原型谷胱甘肽的水平，光动力治疗后肿瘤细胞中会发生铁死亡。总的来说，这项研究为通过谷胱甘肽消耗有效增强光动力疗法提供了一种有效、良好的治疗选择。
A porphyrin-containing nanoscale covalent organic polymer (COP) was fabricated from 5,10,15,20-tetra(4-carboxyphenyl)porphyrin (TCPP) and cystamine via an acylation reaction. On the one hand, TCPP can induce tumor cell death by laser irradiation. Due to the presence of disulfide bonds of cystamine which can react with glutathione, it exhibits depletion of glutathione and accumulation of peroxides in tumor cells. Ultimately by the hyaluronic acid to encapsulate the COP to get S-COP@HA, the nanoparticle with a size of 168.6 nm also exhibits good tumor accumulation and biosafety. Significant inhibition of tumor cell growth was observed after two consecutive doses of S-COP@HA at relatively low laser densities. This combination therapy was proved to reduce the level of reduced glutathione in tumor cells, where ferroptosis occurs after photodynamic treatment. Overall, this study presents a potent, good therapeutic option for the effective enhancement of photodynamic therapy by glutathione depletion.