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

利用超声响应脂质体结合聚焦超声逃避阿霉素诱导的全身免疫抑制

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作者:Jeongjin Lee, Wooram Um, Hyungwon Moon, Hyeyeon Joo, Yeari Song, Minsung Park, Been Yoon, Hyun-Ryoung Kim, Jae Hyung Park

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.

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