光动力疗法
光敏剂
化学
体内
活性氧
癌细胞
铁蛋白
癌症研究
细胞凋亡
生物物理学
肿瘤微环境
体外
细胞生物学
癌症
生物化学
生物
肿瘤细胞
光化学
有机化学
生物技术
遗传学
作者
Mingbo Wu,Wenwu Ling,Jiaojun Wei,Ran Liao,Han Sun,Dongqiu Li,Ye Zhao,Long Zhao
标识
DOI:10.1016/j.jconrel.2022.11.026
摘要
As a novel non-apoptotic cell death pathway, ferroptosis can effectively enhance the antitumor effects of photodynamic therapy (PDT) by disrupting intracellular redox homeostasis. However, the reported nanocomposites that combined the PDT and ferroptosis are cumbersome to prepare, and the unfavorable tumor microenvironment also severely interferes with their tumor suppressive effects. To address this inherent barrier, this study attempted to explore photosensitizers that could activate ferroptosis pathway and found that the photosensitizer aloe-emodin (AE) could induce cellular ferroptosis based on its specific inhibiting activity to Glutathione S-transferase P1(GSTP1), a key protein for ferroptosis. Herein, we prepared [email protected]/Fe nanocrystals (NCs) with synergistic PDT and ferroptosis therapeutic effects by one-step emulsification to obtain AE NCs cores and further modification of red blood cells (RBC) membranes and ferritin. Benefiting from the involvement of ferritin, the prepared [email protected]/Fe NCs provide not only sufficient oxygen for oxygen-dependent PDT, but also Fe3+ for iron-dependent ferroptosis in tumor cells. Furthermore, the biomimetic surface functionalization facilitated the prolonged circulation and cancer targeting of [email protected]/Fe NCs in vivo. The in vitro and in vivo results demonstrate that [email protected]/Fe NCs exhibit significantly enhanced therapeutic effects for the combined two antitumor mechanisms and provide a promising prospect for achieving PDT/ferroptosis synergistic therapy.
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