Multifunctional Nanoparticles for Enhanced Sonodynamic–Chemodynamic Immunotherapy with Glutathione Depletion

Abstract

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.

Keywords::

• chemodynamic therapy
• copper nanoparticles
• immunotherapy
• sonodynamic therapy

Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/nnm-2023-0218

Author contributions

J Song: conceptualization, investigation, data analysis, visualization. C Tang: data analysis; writing (review and editing). Y Wang: data analysis. J Ba: writing (review and editing). K Liu: resources. J Gao: funding. J Chang: funding, supervision. J Kang: conceptualization, supervision, writing (review and editing). L Yin: writing (original draft), supervision.

Acknowledgments

The authors thank R Zhang for his valuable suggestions and constructive comments on the manuscript.

Financial disclosure

This project was financially supported by National Natural Science Foundation of China (grant no. 32271440). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

All animal research procedures were followed in accordance with the standards set forth in the eighth edition of Guide for the Care and Use of Laboratory Animals (published by the National Academy of Sciences, The National Academies Press, Washington, DC), and was approved by the Animal Care Committee of the Faculty of Medicine, Tianjin University (approval no: TJUE-2023-171).

Additional information

Funding

This project was financially supported by National Natural Science Foundation of China (grant no. 32271440). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.