International Journal of Nanomedicine (Nov 2023)

Endogenous H2O2 Self-Replenishment and Sustainable Cascades Enhance the Efficacy of Sonodynamic Therapy

  • Du JR,
  • Teng DK,
  • Wang Y,
  • Wang Q,
  • Lin YQ,
  • Luo Q,
  • Xue JN,
  • Zhu LY,
  • Dong P,
  • Zhang GM,
  • Liu Y,
  • Sun ZX,
  • Wang H,
  • Sui GQ

Journal volume & issue
Vol. Volume 18
pp. 6667 – 6687

Abstract

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Jia-Rui Du, Deng-Ke Teng, Yang Wang, Qimeihui Wang, Yuan-Qiang Lin, Qiang Luo, Jia-Nan Xue, Ling-Yu Zhu, Peng Dong, Gen-Mao Zhang, Yan Liu, Zhi-Xia Sun, Hui Wang,* Guo-Qing Sui* Department of Ultrasound, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Wang; Guo-Qing Sui, Email [email protected]; [email protected]: Sonodynamic therapy (SDT), with its high tissue penetration and noninvasive advantages, represents an emerging approach to eradicating solid tumors. However, the outcomes of SDT are typically hampered by the low oxygen content and immunosuppression in the tumor microenvironment (TME). Accordingly, we constructed a cascade nanoplatform to regulate the TME and improve the anti-tumor efficiency of SDT.Methods: In this study, we rationally design cascade nanoplatform by incorporating immunostimulant hyaluronic acid (HA) and sonosensitizer chlorin e6 (Ce6) on the polydopamine nanocarrier that is pre-doped with platinum nanozymes (designated Ce6/Pt@PDA-HA, PPCH).Results: The cascade reactions of PPCH are evidenced by the results that HA exhibits reversing immunosuppressive that converts M2 macrophages into M1 macrophages in situ, while producing H2O2, and then platinum nanozymes further catalyze the H2O2 to produce O2, and O2 produces abundant singlet oxygen (1O2) under the action of Ce6 and low-intensity focused ultrasound (LIFU), resulting in a domino effect and further amplifying the efficacy of SDT. Due to its pH responsiveness and mitochondrial targeting, PPCH effectively accumulates in tumor cells. Under LIFU irradiation, PPCH effectively reverses immunosuppression, alleviates hypoxia in the TME, enhances reactive oxygen species (ROS) generation, and enhances SDT efficacy for eliminating tumor cells in vivo and in vitro. Meanwhile, an in vivo dual-modal imaging including fluorescence and photoacoustic imaging achieves precise tumor diagnosis.Conclusion: This cascade nanoplatform will provide a promising strategy for enhancing SDT eradication against tumors by modulating immunosuppression and relieving hypoxia.Keywords: tumor microenvironment, tumor-associated macrophages, cascade reactions, sonodynamic therapy, tumor hypoxia

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