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

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Abstract

Chemodynamic therapy (CDT) is well acknowledged as potent reactive oxygen species (ROS)-mediated anticancer strategy. Especially, the study about labile iron pool (LIP) as endogenous ferrous catalyzer has paved the way for future CDT development. However, limited H2O2 expression, mild acidity, reduced glutathione (GSH) ablation of ROS, etc., all require employing alternate peroxo-complex to achieve enhanced CDT effect. As a non-Fenton-type substrate, artesunate (ART) has been utilized as a source of free radicals through decomposition of endoperoxide bridges catalyzed by ferrous ions, nonetheless, the non-tumor-specific delivery, inferior pharmacokinetics, and hydrophobic nature minimize the efficacy of ART in physiological systems. Herein, we devise a PPA nanoamplifier by conjugating ART with PEG-functionalized Pd@Pt nanoplates (PP NPs) to form ester linkage, ensuring specific intratumoral esterase-responsive ART release. Significantly, the PPA nanoamplifier combines the in situ decomposition of ART’s endoperoxide bridges by Fe2+ to superoxide anions (O2·−) and peroxidase (POD)-like enzymatic catalysis of endogenous H2O2 by PP to hydroxyl radicals (·OH), thus achieving amplified ROS-mediated tumor therapy. Besides, PPA displays GSH destruction potential, thereby protecting ROS from the cleavage by GSH oxidation. In addition, the strong absorption of PPA in near-infrared (NIR) region also endows PPA with photoacoustic property to realize imaging-guided CDT. In short, by taking advantages of the high enrichment and esterase- responsive drug release at tumor sites, PPA amplified ROS signals via dual pathways, killing tumor cells in vitro and inhibiting tumor growth in vivo, thereby realizing high-efficiency non-Fenton CDT. We believe our novel anti-tumor strategy based on PPA will broaden the future of ROS-mediated tumor-targeted therapy.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 22075233 and 82073405), and Fundamental Research Funds for the Central Universities (Nos. 20720200020 and 20720190150). We acknowledge the support from Prof. Nanfeng Zheng from Xiamen University.

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  1. Sijin Xiang and Zhongxiong Fan contributed equally to this work.

Authors and Affiliations

  1. College of Chemistry and Chemical Engineering & College of Materials, State Key Laboratory for Physical Chemistry of Solid Surfaces, Research Center for Nano-Preparation Technology of Fujian Province & Key Laboratory of Biomedical Engineering of Fujian Province, Xiamen University, Xiamen, 361005, China

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

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  1. Sijin Xiang
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  2. Zhongxiong Fan
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Correspondence to Zhenqing Hou or Xiaolan Chen.

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

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Xiang, S., Fan, Z., Ye, Z. et al. Endogenous Fe2+-activated ROS nanoamplifier for esterase-responsive and photoacoustic imaging-monitored therapeutic improvement. Nano Res. 15, 907–918 (2022). https://doi.org/10.1007/s12274-021-3574-x

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