Journal
NANO LETTERS
Volume 22, Issue 15, Pages 6156-6165Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.2c01346
Keywords
chemodynamic therapy; autophagy; Prussian blue; curcumin; 5-fluorouracil; colorectal cancer
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Funding
- National Key Research and Development Program of China [2021YFB3801001]
- National Natural Science Foundation of China [32030061]
- Basic Research Program of Shanghai Municipal Government [19JC1415600, 21JC1406000]
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A novel nanomedicine targeting overproduced hydrogen sulfide for precise colorectal cancer therapy has been developed, showing high efficacy in both in vitro and in vivo studies. The nanomedicine utilizes a triple synergistic therapy approach, inducing cell death through chemodynamic therapy and autophagy activation.
Overproduced hydrogen sulfide (H2S) is a highly potential target for precise colorectal cancer (CRC) therapy; herein, a novel 5-Fu/Cur-P@HMPB nanomedicine is developed by coencapsulation of the natural anticancer drug curcumin (Cur) and the clinical chemotherapeutic drug 5-fluorouracil (5-Fu) into hollow mesoporous Prussian blue (HMPB). HMPB with low Fenton-catalytic activity can react with endogenous H2S and convert into high Fenton-catalytic Prussian white (PW), which can generate in situ a high level of .OH to activate chemodynamic therapy (CDT) and meanwhile trigger autophagy. Importantly, the autophagy can be amplified by Cur to induce autophagic cell death; moreover, Cur also acted as a specific chemosensitizer of the chemotherapy drug 5-Fu, achieving a good synergistic antitumor effect. Such a triple synergistic therapy based on a novel nanomedicine has been verified both in vitro and in vivo to have high efficacy in CRC treatment, showing promising potential in translational medicine.
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