期刊
JOURNAL OF CONTROLLED RELEASE
卷 348, 期 -, 页码 590-600出版社
ELSEVIER
DOI: 10.1016/j.jconrel.2022.06.022
关键词
Tumor metastasis; Starvation-phototherapy; Lactate; Mitochondrial dysfunction; Hypoxia
资金
- Guangdong Basic and Applied Basic Research Foundation [2019B030302012]
- National Key Research and Development Project [2020YFA0509400]
- National NaturalScience Foundation of China [82130082, 81821002, 81790251]
Lactate and mitochondria are closely related to tumor proliferation and metastasis. A new research direction combines lactate deprivation with mitochondria-targeted phototherapy to achieve a safer and more effective strategy against tumor metastasis.
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/MOS@M780 & 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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