Biodegradable Ca-MOF Nanoplatform with Intracellular H2O2-Triggered CO Release to Augment Mitochondrial Ca2+ Overload for Synergistic Cancer Therapy.

IF 4.7 2区化学 Q1 CHEMISTRY, INORGANIC & NUCLEAR

Inorganic Chemistry Pub Date : 2025-09-23 DOI:10.1021/acs.inorgchem.5c04034

Jian An,Yan Miao,Yawen Xu,Yuxing Huang,Heng Wang,Jin Wang,Yan Cai,Tingting Chen,Yong Yao,Yang Wang

引用次数: 0

Abstract

To address the challenges of precise calcium regulation and limited efficacy in MOF-based nanomedicine, we developed a biodegradable Ca-MOF platform (Ca-MOF@MnCO/HA) coated with hyaluronic acid (HA) and loaded with a H2O2-responsive CO prodrug, manganese carbonyl (MnCO). This system enables CD44-mediated tumor targeting, followed by acid-triggered biodegradation in the tumor microenvironment (TME) to release Ca2+ and MnCO. Intracellular H2O2 then promotes CO release, inducing mitochondrial dysfunction and impairing calcium efflux. The concurrent release of Ca2+ and CO causes sustained calcium overload, intensifying oxidative stress, activating apoptosis, and triggering tumor-specific calcification. This gas-ion synergy highlights the potential of programmable inorganic nanomedicines for improved anticancer therapy.

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生物可降解的Ca-MOF纳米平台与细胞内h2o2触发的CO释放增加线粒体Ca2+超载的协同癌症治疗。

为了解决基于mof的纳米药物中钙的精确调节和有限疗效的挑战，我们开发了一种可生物降解的Ca-MOF平台（Ca-MOF@MnCO/HA），该平台包被透明质酸（HA），并负载h2o2响应的CO前药锰羰基（MnCO）。该系统启用cd44介导的肿瘤靶向，随后在肿瘤微环境（TME）中酸触发的生物降解释放Ca2+和MnCO。然后，细胞内H2O2促进CO释放，诱导线粒体功能障碍并损害钙外排。Ca2+和CO的同时释放导致持续的钙超载，加剧氧化应激，激活细胞凋亡，并触发肿瘤特异性钙化。这种气体-离子协同作用突出了可编程无机纳米药物在改善抗癌治疗方面的潜力。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Inorganic Chemistry 化学-无机化学与核化学

CiteScore

7.60

自引率

13.00%

发文量

1960

审稿时长

1.9 months

期刊介绍： Inorganic Chemistry publishes fundamental studies in all phases of inorganic chemistry. Coverage includes experimental and theoretical reports on quantitative studies of structure and thermodynamics, kinetics, mechanisms of inorganic reactions, bioinorganic chemistry, and relevant aspects of organometallic chemistry, solid-state phenomena, and chemical bonding theory. Emphasis is placed on the synthesis, structure, thermodynamics, reactivity, spectroscopy, and bonding properties of significant new and known compounds.