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

Ju Huang; Liang Zhang; Jun Zheng; Yi Lin; Xiaojing Leng; Chunjie Wang; Pan Li; Liangzhu Feng

doi:10.1016/j.biomaterials.2023.122181

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

Biomaterials. 2023 Aug:299:122181. doi: 10.1016/j.biomaterials.2023.122181. Epub 2023 Jun 1.

Authors

Ju Huang¹, Liang Zhang², Jun Zheng¹, Yi Lin³, Xiaojing Leng¹, Chunjie Wang⁴, Pan Li⁵, Liangzhu Feng⁶

Affiliations

¹ Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China.
² Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China; Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, PR China.
³ Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400042, PR China.
⁴ Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, 199 Ren' Ai Road, Suzhou, Jiangsu, 215123, PR China.
⁵ Chongqing Key Laboratory of Ultrasound Molecular Imaging, Institute of Ultrasound Imaging, Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, PR China. Electronic address: lipan@hospital.cqmu.edu.cn.
⁶ Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, 199 Ren' Ai Road, Suzhou, Jiangsu, 215123, PR China. Electronic address: lzfeng@suda.edu.cn.

PMID: 37276797
DOI: 10.1016/j.biomaterials.2023.122181

Abstract

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.

Keywords: Enhanced cancer treatment; Enhanced tumor accumulation; Microbubble-assisted ultrasonication technology; Tumor microenvironment modulation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents* / therapeutic use
Cell Line, Tumor
Doxorubicin
Humans
Microbubbles
Neoplasms* / drug therapy
Tumor Microenvironment

Substances

Doxorubicin
Antineoplastic Agents