Endogenous Fe2+-activated ROS nanoamplifier for esterase-responsive and photoacoustic imaging-monitored therapeutic improvement

Xiang, Sijin; Fan, Zhongxiong; Ye, Zichen; Zhu, Tianbao; Shi, Dao; Ye, Shefang; Hou, Zhenqing; Chen, Xiaolan

doi:10.1007/s12274-021-3574-x

Cited by 24 publications

(7 citation statements)

References 52 publications

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“…The limitations of smallmolecule chemotherapeutic drugs, such as insufficient water solubility, low bioavailability, and toxic effects on normal tissues, lead to drug resistance, poor efficacy, metastasis, and undesirable side effects. [1] Various nanoplatforms have been developed for efficient drug delivery to the tumor site to enhance its therapeutic efficacy and reduce its toxic side effects including inorganic nanosystems, [2] metal-phenolic networks, [3] micelles, [4] liposomes, [5] dendrimers, [6] and nanogels. [7] However, few nanoplatforms are available for clinical investigation mainly due to the defects including poor drug loading efficacy, potential systematic toxicity and immunogenicity, multi-step synthetic processes, and complex components and structure.…”

Section: Introductionmentioning

confidence: 99%

Gossypol‐Crosslinked Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Ultrasound‐Enhanced Precision Tumor Theranostics

Yang

Zhang

et al. 2023

Advanced Sensor Research

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Development of tumor microenvironment (TME)‐responsive nanomedicines with simple components for precision tumor theranostics still maintains a great challenge. Here, the design of an intelligent nanocluster (NC) system assembled from gossypol‐mediated crosslinking of phenylboronic acid‐modified ultrasmall iron oxide nanoparticles (USIO NPs) is presented. The gossypol functions as both a chemotherapy (CT) drug and a crosslinker through phenylborate ester bonds that are sensitive to both reactive oxygen species (ROS) and pH. The developed gossypol‐USIO NCs (for short, G‐USIO NCs), having a size of 34.2 nm, possess stability under physiological conditions, enable intracellular ROS generation and glutathione depletion to modulate TME, promote apoptosis of cancer cells in vitro, and inhibit tumor/lung metastasis in vivo through gossypol‐mediated CT and USIO‐mediated chemodynamic therapy owing to the ROS‐ and pH‐triggered dissociation of the NCs to release gossypol and Fe at the tumor site. Likewise, the dissociated USIO NPs from the NCs afford TME‐facilitated T1‐weighted magnetic resonance (MR) imaging. Furthermore, the effects of the tumor T1 MR imaging and the combination therapy can be elevated by ultrasound‐targeted microbubble destruction‐induced cavitation and sonoporation. The designed G‐USIO NCs with simple ingredients are likely developed to be a promising theranostic nanomedicine formulation for ultrasound‐facilitated precision theranostics of various tumor types.

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Section: Introductionmentioning

confidence: 99%

Gossypol‐Crosslinked Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Ultrasound‐Enhanced Precision Tumor Theranostics

Yang

Zhang

et al. 2023

Advanced Sensor Research

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“…The •OH production ability of 3‐AT&MA@FHM was investigated by the TMB assay. The TMB could be oxidized to form a blue ox TMB in the presence of •OH, which has obvious absorption peaks at 371 and 652 nm, the color was blue or yellow, [ 20 ] and the mechanism was shown in Figure 4G. The •OH produced by the Fenton reaction oxidized the amino group of TMB into colored substances.…”

Section: Resultsmentioning

confidence: 99%

Multifunctional Iron‐Doped Hollow Mesoporous Silica Nanoregulator for Enhanced Tumor Chemodynamic Therapy

Ling,

Wang,

et al. 2023

Part & Part Syst Charact

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Chemodynamic therapy (CDT) is a promising method that uses endogenous hydrogen peroxide (H2O2) to produce cytotoxic hydroxyl radicals (•OH) via Fenton reaction to kill tumor cells. However, the insufficient contents of H2O2 and the presence of glutathione (GSH) can significantly reduce the therapeutic effect of CDT. Herein, a multifunctional nanoregulator (3‐AT&MA@FHM) that combines Fe‐doped hollow mesoporous silica nanoparticles (Fe‐doped hMSN, or FHM) with 3‐amino‐1,2,4‐triazole (3‐AT) and maleimide (MA) are developed to overcome these challenges. After endocytosis by tumor cells, FHM part of the nanoregulator degrades in a mildly acidic intracellular environment and releases Fe3+ for CDT. The subsequently released 3‐AT serves as a catalase inhibitor to promote the accumulation of H2O2, while MA acts as a GSH scavenger to decrease the GSH content in tumor cells. This multifunctional nanoplatform simultaneously regulates the contents of H2O2‐the substrate for Fenton reaction and GSH‐the main antioxidant, resulting in a significantly enhanced CDT effect. Moreover, organoids are used for safety and toxicity evaluation. The results of organoids experiments showed similar trends to those of cellular experiments, but MIO is more resistant to stress than cells. This study is expected to provide a novel idea for the design of highly efficient CDT nanosystems.

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“…, artesunate (ART)) have been selected as a source of ˙O 2 − through the Fe 2+ -catalyzed breakdown of endoperoxide bridges, where a nanoamplifier attached to ART combined with in situ Fe 2+ decomposed the endoperoxide bridge of ART to ˙O 2 − . 141,142…”

Section: Design Of Ros Generation and Upregulation Systemsmentioning

confidence: 99%

Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy

et al. 2023

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Endogenous Fe2+-activated ROS nanoamplifier for esterase-responsive and photoacoustic imaging-monitored therapeutic improvement

Cited by 24 publications

References 52 publications

Gossypol‐Crosslinked Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Ultrasound‐Enhanced Precision Tumor Theranostics

Gossypol‐Crosslinked Nanoclusters of Ultrasmall Iron Oxide Nanoparticles for Ultrasound‐Enhanced Precision Tumor Theranostics

Multifunctional Iron‐Doped Hollow Mesoporous Silica Nanoregulator for Enhanced Tumor Chemodynamic Therapy

Reactive oxygen species-upregulating nanomedicines towards enhanced cancer therapy

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