Chen Laura E, Nittayacharn Pinunta, Exner Agata A
Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USA.
Department of Radiology, Case Western Reserve University, Cleveland, OH, USA.
Expert Opin Drug Deliv. 2025 Jul;22(7):1007-1030. doi: 10.1080/17425247.2025.2505044. Epub 2025 May 18.
Despite much progress, nanomedicine-based drug therapies in oncology remain limited by systemic toxicity and insufficient particle accumulation in the tumor. To address these barriers, formulations responsive to external physical stimuli have emerged. One most promising system is the ultrasound stimulation of drug-loaded, gas-core particles (bubbles). Ultrasound induces bubble cavitation for cell and tissue permeabilization, triggers on-demand drug release, and provides opportunities for real-time imaging of delivery.
Here, we focus on shell-stabilized, gas-core nanoparticles (also termed nanobubbles or ultrafine bubbles) and their role in ultrasound-mediated therapeutic delivery to tumors. This review frames the advantages of nanobubbles within the ongoing deficits in nanomedicine, describes mechanisms of ultrasound-mediated therapy, and details formulation techniques for nanobubble delivery systems. It then highlights the past decade of research in nanobubble-facilitated drug delivery for cancer therapy and anticipates new directions in the field.
Nanobubble ultrasound contrast agents offer a spatiotemporally triggerable therapeutic coupled with a safe, accessible imaging modality. Nanobubbles can be loaded with diverse therapeutic cargoes to treat disease and overcome numerous barriers limiting delivery to solid tumors. Close attention to formulation, characterization methods, acoustic testing parameters, and the biological mechanisms of nanobubble delivery will facilitate preclinical research toward clinical adoption.
尽管取得了很大进展,但基于纳米医学的肿瘤药物治疗仍受到全身毒性和肿瘤内颗粒积累不足的限制。为了克服这些障碍,对外部物理刺激有响应的制剂应运而生。最有前景的系统之一是对负载药物的气核颗粒(气泡)进行超声刺激。超声可诱导气泡空化,实现细胞和组织通透化,触发按需释药,并为递送过程提供实时成像的机会。
在此,我们重点关注壳层稳定的气核纳米颗粒(也称为纳米气泡或超细气泡)及其在超声介导的肿瘤治疗递送中的作用。本综述阐述了纳米气泡在纳米医学现有不足中的优势,描述了超声介导治疗的机制,并详细介绍了纳米气泡递送系统的制剂技术。随后重点介绍了过去十年中纳米气泡促进癌症治疗药物递送的研究情况,并展望了该领域的新方向。
纳米气泡超声造影剂提供了一种时空可控的治疗方法,并结合了一种安全、便捷的成像方式。纳米气泡可以装载多种治疗药物来治疗疾病,并克服限制向实体瘤递送的众多障碍。密切关注纳米气泡递送的制剂、表征方法、声学测试参数和生物学机制,将有助于推进临床前研究以实现临床应用。