Evading Doxorubicin-Induced Systemic Immunosuppression Using Ultrasound-Responsive Liposomes Combined with Focused Ultrasound

Pharmaceutics. 2022 Nov 25;14(12):2603. doi: 10.3390/pharmaceutics14122603.

Abstract

Doxorubicin (DOX) is a representative anticancer drug with a unique ability to induce immunogenic cell death of cancer cells. However, undesired toxicity on immune cells has remained a significant challenge, hindering the usage of DOX in cancer immunotherapy. Here, we report a combined therapy to avoid the off-target toxicity of DOX by adapting ultrasound-responsive liposomal doxorubicin and focused ultrasound exposure. Histological analysis demonstrated that the combined therapy induced less hemosiderosis of splenocytes and improved tumor infiltration of cytotoxic T lymphocytes. Additionally, in vivo therapeutic evaluation results indicate that the combined therapy achieved higher efficacy when combined with PD-1 immune-checkpoint blockade therapy by improving immunogenicity.

Keywords: cancer immunotherapy; doxorubicin; immune checkpoint blockade; immunogenic cell death.

Grants and funding

This work was supported by the Biohealth Technology Development Program (20018412, Development of ultrasound-sensitive drug delivery system for treatment of cancer) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).