Drug-loaded hybrid hydrogels for sonodynamic-chemodyanmic therapy and tumor metastasis suppression

Xiaoying Wang; Liyun Zhu; Jianhui Zhou; Lingzhou Zhao; Jingchao Li; Changcun Liu

doi:10.3389/fbioe.2023.1281157

Drug-loaded hybrid hydrogels for sonodynamic-chemodyanmic therapy and tumor metastasis suppression

Front Bioeng Biotechnol. 2023 Sep 18:11:1281157. doi: 10.3389/fbioe.2023.1281157. eCollection 2023.

Authors

Xiaoying Wang^#¹, Liyun Zhu^#², Jianhui Zhou², Lingzhou Zhao³, Jingchao Li², Changcun Liu³

Affiliations

¹ Office of Hospital Infection and Disease Control and Prevention, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
² College of Biological Science and Medical Engineering, Donghua University, Shanghai, China.
³ Department of Nuclear Medicine, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

^# Contributed equally.

Abstract

Introduction: Although various therapies have been adopted to treat cancer, metastasis of tumor cells still is a big challenge that compromises therapeutic benefits. Methods: We herein report an injectable drug-loaded hybrid hydrogel that can achieve sonodynamic therapy (SDT) and chemodyanmic therapy (CDT) combined action and suppression of tumor metastasis. This alginate (ALG)-based hydrogel (termed as AMPS) contains manganese dioxide (MnO₂) nanoparticles as the CDT agents, an organic polymer as the sonosensitizer, and a SIS3 drug as metastasis inhibitor. Results: AMPS is formed via the chelation of ALG by Ca²⁺ in tumor microenvironment, in which MnO₂ nanoparticles mediate CDT via Fenton-like reaction and the organic polymers enable SDT under ultrasound (US) irradiation by generating singlet oxygen (¹O₂), allowing for combinational action of CDT and SDT. In addition, SIS3 is released from AMPS hydrogels to inhibit the metastasis of tumor cells. As such, the AMPS enables a combinational action of SDT and CDT to greatly inhibit the growths of subcutaneous tumors in living mice and also completely suppress the tumor metastasis in lungs and livers. Conclusion: This study thus offers a hybrid hydrogel platform for combinational therapy and metastasis suppression simultaneously.

Keywords: alginate hydrogels; chemodyanmic therapy; drug delivery; sonodynamic therapy; tumor metastasis.

Grants and funding

The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was financially supported by the key scientific and technological project of Songjiang District (21SJKJGG155) and Fundamental Research Funds for the Central Universities (2232021A-05).