期刊
NANO LETTERS
卷 19, 期 2, 页码 805-815出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b03905
关键词
GA-Fe(II) nanocomplexes; Fenton reaction; GSH depletion; disruption of redox homeostasis; cancer combination therapy
类别
资金
- National Research Programs from Ministry of Science and Technology (MOST) of China [2016YFA0201200]
- National Natural Science Foundation of China [51525203, 51761145041, 51802209]
- Natural Science Foundation of Jiangsu Province [BK20180848]
- China Postdoctoral Science Foundation [2017M610348, 2018T110545]
- Collaborative Innovation Center of Suzhou Nano Science and Technology
- 111 Program from the Ministry of Education of China
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
Amplification of intracellular oxidative stress has been found to be an effective strategy to induce cancer cell death. To this end, we prepare a unique type of ultrasmall gallic acid-ferrous (GA-Fe(II)) nanocomplexes as the catalyst of Fenton reaction to enable persistent conversion of H2O2 to highly cytotoxic hydroxyl radicals (center dot OH). Then, both GA-Fe(II) and L-buthionine sulfoximine (BSO), an inhibitor of glutathione (GSH) synthesis, are coencapsulated within a stealth liposomal nanocarrier. Interestingly, the obtained BSO/GA-Fe(II)@liposome is able to efficiently amplify intracellular oxidative stress via increasing center dot OH generation and reducing GSH biosynthesis. After chelating with Tc-99m(4+) radioisotope, such BSO/GA-Fe(II)@ liposome could be tracked under in vivo single-photon-emission-computed-tomography (SPECT) imaging, which illustrates the time-dependent tumor homing of such liposomal nanoparticles after intravenous injection. With GA-Fe(II)-mediated center dot OH production and BSO-mediated GSH depletion, treatment with such BSO/GA-Fe(II)@liposome would lead to dramatically enhanced intratumoral oxidative stresses, which then result in remarkably improved therapeutic efficacies of concurrently applied chemotherapy or radiotherapy. This work thus presents the concise fabrication of biocompatible BSO/GA-Fe(II)@ liposome as an effective adjuvant nanomedicine to promote clinically used conventional cancer chemotherapy and radiotherapy, by greatly amplifying the intratumoral oxidative stress.
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