MOLECULAR PHARMACEUTICS
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2023
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IF 4.9
Zhaomin Tang,Shuting Jiang,Wanlan Tang,Qian He,Huangzhao Wei,Chengyu Jin,Shuai Wang,Hui Zhang
Chemodynamic therapy (CDT) that involves the use of Fenton catalysts to convert endogenous hydrogen peroxide (H2O2) to hydroxyl radicals (·OH) constitutes a promising strategy for cancer therapy; however, insufficient endogenous H2O2 and glutathione (GSH) overexpression render its efficiency unsatisfactory. Herein, we present an intelligent nanocatalyst that comprises copper peroxide nanodots and DOX-loaded mesoporous silica nanoparticles (MSNs) (DOX@MSN@CuO2) and can self-supply exogenous H2O2 and respond to specific tumor microenvironments (TME). Following endocytosis into tumor cells, DOX@MSN@CuO2 initially decomposes into Cu2+ and exogenous H2O2 in the weakly acidic TME. Subsequently, Cu2+ reacts with high GSH concentrations, thereby inducing GSH depletion and reducing Cu2+ to Cu+ Next, the generated Cu+ undergoes Fenton-like reactions with exogenous H2O2 to accelerate toxic ·OH production, which exhibits a rapid reaction rate and is responsible for tumor cell apoptosis, thereby enhancing CDT. Furthermore, the successful delivery of DOX from the MSNs achieves chemotherapy and CDT integration. Thus, this excellent strategy can resolve the problem of insufficient CDT efficacy due to limited H2O2 and GSH overexpression. Integrating H2O2 self-supply and GSH deletion enhances CDT, and DOX-induced chemotherapy endows DOX@MSN@CuO2 with effective tumor growth-inhibiting properties alongside minimal side effects in vivo.
研究领域:
肿瘤学
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生物医学工程
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药理学
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2025
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IF 4.6
Xiang-Cheng Lin,Jian Liu,Miaomiao Hu,Lingjun Song,Minzhe Li,Qinjie Kou,Rong Huang,Lixian Sun,Changchun Wen
The abnormal fluctuations of glutathione (GSH) in vivo often reflect disease progression and are closely linked to human metabolism and physiological functions. Highly sensitive and selective detection of GSH is crucial for guiding early diagnosis and treatment; however, achieving this remains a significant challenge. In this study, we developed an enzyme activity sensor platform for the efficient detection of GSH. This platform utilizes Au@CuS core–shell materials loaded with CuO 2 nanoparticles to create a composite nanosensor system. Under slightly acidic conditions, CuO 2 on the nanomaterial’s surface decomposes into H 2 O 2 and Cu 2+ ions. The generated H 2 O 2 then reacts with tetramethylbenzidine (TMB) in the presence of peroxidase-like CuS to yield oxidized tetramethylbiphenyl ( OX TMB), which generates a distinctive Raman signal. Upon addition of GSH to the system, the unique OX TMB signal diminishes due to GSH’s strong antioxidant capacity and the consequent consumption of OX TMB. This sensing method enables sensitive detection of GSH, with a detection limit as low as 1.2 × 10 -13 mol∙L -1 . This approach holds promise for providing researchers with rapid and precise in vitro analysis of GSH, serving as an indicator for early disease diagnosis and real-time evaluation of treatment efficacy.
研究领域:
生物化学
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纳米医学
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诊断学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2025
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IF 8.2
Huiru Zhu,Xiaoying Ni,Jiaxin Su,Yong Qin,Xiaoya He,Bo Liu,Shuang Ding,Haoru Wang,Xiangmin Zhang,Jie Huang,Qian Hu,Ruofei Ma,Jinhua Cai
To overcome the limited efficacy of chemodynamic therapy (CDT) caused by insufficient hydrogen peroxide (H2O2) in the tumor microenvironment, we engineered a glutathione (GSH)-responsive multifunctional nanosystem, HCTG-C, based on hollow mesoporous organosilica nanoparticles. This system integrates tirapazamine (TPZ), glucose oxidase (GOx), in situ-synthesized copper sulfide (CuS), and CT2A glioma cell membrane coating to enable dual tumor-targeted therapy and self-imaging capabilities. The therapeutic mechanism relies on three synergistic cascades: (1) GOx-mediated glucose oxidation to deplete oxygen and generate H2O2, establishing a self-sustaining H2O2 supply; (2) GSH-triggered CuS conversion to Cu(I), amplifying Fenton-like reactions for efficient H2O2-to-reactive oxygen species conversion and ferroptosis induction; and (3) hypoxia-activated TPZ to exert cytotoxic effects, synergizing chemotherapy with CDT. Experimental results demonstrated that HCTG-C achieves real-time MRI monitoring via GSH depletion-driven Cu valence transitions, while its self-replenishing H2O2 and oxygen-activation mechanisms significantly enhance antitumor efficacy against CT2A glioma in vitro and in vivo. By innovatively combining H2O2 self-supply cascades, hypoxia-activated chemotherapy, and ferroptosis-driven CDT, this work presents a paradigm-shifting strategy for self-imaging-guided combinatorial therapy, advancing ferroptosis-based approaches for precision glioma treatment.
研究领域:
纳米医学
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肿瘤治疗
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影像学
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生物材料
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产品关联
DOI
PubMed
高影响因子
Advanced Science
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2024
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IF 14.3
Huiyan Du,Ensheng Xu,Yihan Xu,Qingwang Xue,Hongxia Xu,Jibin Song
The development of theragnostic nanosystems integrating FRET (fluorescence resonance energy transfer) imaging and chemodynamic therapy (CDT) for accurate diagnosis and effective treatment of lung tumors is still a big challenge. Herein, a peptide-assembled 3D DNAzyme motor nanodevice is engineered for a self-powered FRET amplifier profiling human neutrophil elastase (HNE) and self-supplied H 2 O 2 enhancing CDT. The nanodevice is prepared by depositing AuNPs on ZIF-8, in which ZIF-8 co-loaded the lysosomal targeting peptide-modified copper peroxides (PCPs) and hairpins (H1, H2, and H3), AuNPs are co-labeled by DNAzyme-peptide (DP) conjugate and H3. In the tumor micro-environment, HNE driven 3D DNAzyme walker followed by an exponential amplification constructed by a synergistic cross-activation between hybridization chain reaction and DNAzyme, generating a self-powered FRET amplifier. The FRET amplifier specifically measures HNE with a sensitivity of 0.026 pM, and successfully images exogenous HNE in living cells and monitors HNE in mouse models. Moreover, the PCPs can target lysosomes, reducing lysosome escape. The self-supplying H 2 O 2 undertaken by PCPs improves the Cu (II)-catalyzed Fenton-like reaction, effectively causing cell apoptosis to inhibit tumor growth. Significantly, the nanodevice successfully screens inhibitors and discriminates the HNE level in normal and lung cancer tissues, suggesting that the nanodevice provides an effective tool for the diagnosis and treatment of lung tumors.
研究领域:
纳米技术
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癌症诊断与治疗
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
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