肿瘤微环境
化学
线粒体
转移
透明质酸
生物化学
缺氧(环境)
新陈代谢
瓦博格效应
癌症研究
共轭亚油酸
活性氧
亚油酸
细胞生物学
糖酵解
癌症
生物
脂肪酸
氧气
内科学
医学
遗传学
有机化学
肿瘤细胞
作者
Hailong Tian,Li Zhou,Yu Wang,Edouard C. Nice,Canhua Huang,Haiyuan Zhang
标识
DOI:10.1016/j.jconrel.2022.06.022
摘要
Recently, lactate has been considered as an alternative direct energy substance to glucose for tumor proliferation and metastasis. Meanwhile, mitochondria, as important energy-supplying organelles, are also closely related to tumor progression. Consequently, a new research direction for lactate comprises lactate deprivation coupled with mitochondria-targeted phototherapy to achieve a safer and more effective strategy against tumor metastasis. Herein, linoleic acid-conjugated hyaluronic acid (HL), disulfide bond-rich nanovehicle (mesoporous silica, MOS), mitochondria-targeted IR780 (M780) and lactate oxidase (LOD) are rationally designed as a specific-targeting metabolism nanomodulator (HL/[email protected]&LOD NPs), fulfilling the task of simultaneous depriving cells of lactate and damaging mitochondria to prevent tumor metastasis. Interestingly, M780-mediated photodynamic therapy (PDT) and LOD-mediated starvation therapy can effectively exacerbate the hypoxia state of tumor cells, thereby increasing the free iron levels to activate ferroptosis. On one hand, pyruvic acid and H2O2 generated by LOD-mediated lactate metabolism can provide powerful conditions for iron-catalyzed ferroptosis. On the other, the depleted GSH and increased reactive oxygen species (ROS) can oxidize linoleic acid into lipid peroxides (LPO) to further augment ferroptosis. The designed nanomodulator therefore shows great promise for fighting tumor metastasis by manipulating energy metabolism and the hypoxia microenvironment.
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