Enhanced ferroptosis by a nanoparticle mimicking hemoglobin coordinate pattern with self-supplying hydrogen peroxide

Insufficient endogenous H2O2 for generation of hydroxyl radicals (•OH) has strikingly compromised anti-tumor benefits of ferroptosis. Herein, we develop a H2O2 self-supplying nanoparticle based on a pH-responsive lipopeptide C18-pHis10. Inspired by the coordinate pattern of hemoglobin binding heme,...

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Bibliographic Details
Published in:Chinese chemical letters 2024-06, p.110097, Article 110097
Main Authors: Gao, Yan, Song, Zi-Lin, Yu, Shuang, Zhao, Xiu-Li, Chen, Da-Wei, Qiao, Ming-Xi
Format: Article
Language:English
Subjects:
Coordination-assembly
Ferroptosis
Functionalized lipopeptide
H2O2 self-supply
Hemoglobin-mimicking
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Summary:Insufficient endogenous H2O2 for generation of hydroxyl radicals (•OH) has strikingly compromised anti-tumor benefits of ferroptosis. Herein, we develop a H2O2 self-supplying nanoparticle based on a pH-responsive lipopeptide C18-pHis10. Inspired by the coordinate pattern of hemoglobin binding heme, Fe2+ and tetrakis (4-carboxyphenyl) porphyrin (TCPP) were delicately encapsulated by formation of coordination compounds with His. Ascorbgyl palmitate (AscP) was also incorporated into the nanoparticles for generation of H2O2 by reduction 1O2 produced from TCPP, meanwhile prevented Fe2+ from being oxidized. The protonation of pHis in acidic endo-lysosome induced the breakage of Fe2+/His/TCPP coordinate interactions, leading to accelerated release of payloads and the following escape to cytoplasm. Upon laser irradiation, TCPP produces excessive 1O2 followed by conversion to H2O2 in the presence of AscP, which is further catalyzed to lethal •OH by Fe2+via Fenton reaction. The self-supplying H2O2 was found to result significantly higher accumulation of lipid peroxides and more effective tumor inhibition. Overall, this work sheds new a light on H2O2 self-supplying strategy to enhance ferroptosis by taking advantage of 1O2 generated by photodynamic therapy (PDT). [Display omitted] This study proposed a novel H2O2 self-supplying approach by taking advantage of conversing H2O2 from 1O2 generated by PDT to boost ferroptosis, by virtue of a coordination-assembled nanoparticle based on the pH-responsive lipopeptide C18-pHis10 to co-encapsulate ascorbgyl palmitate, Fe2+, and TCPP.
ISSN:1001-8417
1878-5964
DOI:10.1016/j.cclet.2024.110097