Proton nanomodulators for enhanced Mn2+-mediated chemodynamic therapy of tumors via HCO3− regulation.

Autor: Yang, Peng, Liu, Shaojie, Chen, Zhuang, Liu, Weijing, Duan, Deshang, Yang, Zuo, Yan, Haohao, Rao, Zhiping, Zhang, Xianghan, Zhang, Ruili, Wang, Zhongliang
Předmět:
Zdroj: Journal of Nanobiotechnology; 11/1/2024, Vol. 22 Issue 1, p1-13, 13p
Abstrakt: Background: Mn2+-mediated chemodynamic therapy (CDT) has been emerged as a promising cancer therapeutic modality that relies heavily on HCO3− level in the system. Although the physiological buffers (H2CO3/HCO3−) provide certain amounts of HCO3−, the acidity of the tumor microenvironment (TME) would seriously affect the HCO3− ionic equilibrium (H2CO3 ⇌ H+ + HCO3−). As a result, HCO3− level in the tumor region is actually insufficient to support effective Mn2+-mediated CDT. Results: In this study, a robust nanomodulator MnFe2O4@ZIF-8 (PrSMZ) with the capability of in situ self-regulation HCO3− is presented to enhance therapeutic efficacy of Mn2+-mediated CDT. Under an acidic tumor microenvironment, PrSMZ could act as a proton sponge to shift the HCO3− ionic equilibrium to the positive direction, significantly boosting the generation of the HCO3−. Most importantly, such HCO3− supply capacity of PrSMZ could be finely modulated by its ZIF-8 shell thickness, resulting in a 1000-fold increase in reactive oxygen species (ROS) generation. Enhanced ROS-dependent CDT efficacy is further amplified by a glutathione (GSH)-depletion ability and the photothermal effect inherited from the inner core MnFe2O4 of PrSMZ to exert the remarkable antitumor effect on mouse models. Conclusions: This work addresses the challenge of insufficient HCO3− in the TME for Mn2+-mediated Fenton catalysts and could provide a promising strategy for designing high-performance Mn2+-mediated CDT agents to treat cancer effectively. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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