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Research Article

Multifunctional nanoparticles for enhanced sonodynamic–chemodynamic immunotherapy with glutathione depletion

    Jianying Song‡

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    ‡Authors contributed equally

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    ,
    Cong Tang‡

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    ‡Authors contributed equally

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    ,
    Yun Wang‡

    Xuzhou Central Hospital, Xuzhou, Jiangsu Province, 221009, China

    ‡Authors contributed equally

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    ,
    Junli Ba

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    ,
    Kairui Liu

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    ,
    Jinwei Gao

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    ,
    Jin Chang

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    ,
    Jun Kang

    *Author for correspondence:

    E-mail Address: jun.kang@tju.edu.cn

    School of Life Sciences, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China

    &
    Linling Yin

    **Author for correspondence:

    E-mail Address: yinlinling@sjtu.edu.cn

    Department of stomatology, Shanghai General Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 200080, China

    Published Online:https://doi.org/10.2217/nnm-2023-0218

    Aim: This study aimed to develop a sonodynamic–chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper–cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4+ and CD8+ T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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