Microbubbles-assisted ultrasonication to promote tumor accumulation of therapeutics and modulation of tumor microenvironment for enhanced cancer treatments

• Published in: Biomaterials 2023-08, Vol.299, p.122181-122181, Article 122181
• Main Authors: Huang, Ju, Zhang, Liang, Zheng, Jun, Lin, Yi, Leng, Xiaojing, Wang, Chunjie, Li, Pan, Feng, Liangzhu
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - therapeutic use; Cell Line, Tumor; Doxorubicin; Enhanced cancer treatment; Enhanced tumor accumulation; Humans; Microbubble-assisted ultrasonication technology; Microbubbles; Neoplasms - drug therapy; Tumor Microenvironment; Tumor microenvironment modulation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2023.122181

Abnormal tumor vasculature is reported to severely hinder the therapeutic potency of diverse cancer therapeutics by restricting their intratumoral accumulation and/or causing therapeutic resistance. Herein, a microbubble-assisted ultrasonication technology (MAUT) of systemic administration of octafluoropropane-filled microbubbles together with tumor localized ultrasound (US) exposure is developed to generally promote intratumoral accumulation efficacy of three kinds of anti-tumor drugs with varying sizes through the cavitation effect-induced disruption of tumor blood vessels. MAUT was further shown to enable selective tumor hypoxia attenuation by filling microbubbles with high-purity oxygen and thus reducing the production of immunosuppressive lactic acids by suppressing glycolysis in cancer cells. Resultantly, MAUT markedly enhanced the therapeutic outcome of systemically administered anti-programmed death-1 (anti-PD-1) and chemotherapeutic doxorubicin (DOX) with and without using nanoscale liposomes as delivery vehicles. This work highlights that MAUT is a biocompatible yet versatile strategy to effectively reinforce the therapeutic potency of a broad range of cancer therapeutics, promising for future clinical usage.