Wu Qiuyu, Xia Yuanhang, Xiong Xiaohe, Duan Xinxing, Pang Xiaoxiao, Zhang Fugui, Tang Song, Su Junlei, Wen Shuqiong, Mei Li, Cannon Richard D, Ji Ping, Ou Zhanpeng
Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing Medical University, Chongqing, China.
Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Medical University, Chongqing, China.
Front Pharmacol. 2023 Apr 26;14:1169608. doi: 10.3389/fphar.2023.1169608. eCollection 2023.
In the last decade, immune checkpoint blockade (ICB) has revolutionized the standard of treatment for solid tumors. Despite success in several immunogenic tumor types evidenced by improved survival, ICB remains largely unresponsive, especially in "cold tumors" with poor lymphocyte infiltration. In addition, side effects such as immune-related adverse events (irAEs) are also obstacles for the clinical translation of ICB. Recent studies have shown that focused ultrasound (FUS), a non-invasive technology proven to be effective and safe for tumor treatment in clinical settings, could boost the therapeutic effect of ICB while alleviating the potential side effects. Most importantly, the application of FUS to ultrasound-sensitive small particles, such as microbubbles (MBs) or nanoparticles (NPs), allows for precise delivery and release of genetic materials, catalysts and chemotherapeutic agents to tumor sites, thus enhancing the anti-tumor effects of ICB while minimizing toxicity. In this review, we provide an updated overview of the progress made in recent years concerning ICB therapy assisted by FUS-controlled small-molecule delivery systems. We highlight the value of different FUS-augmented small-molecules delivery systems to ICB and describe the synergetic effects and underlying mechanisms of these combination strategies. Furthermore, we discuss the limitations of the current strategies and the possible ways that FUS-mediated small-molecule delivery systems could boost novel personalized ICB treatments for solid tumors.
在过去十年中，免疫检查点阻断（ICB）彻底改变了实体瘤的治疗标准。尽管在几种免疫原性肿瘤类型中取得了成功，生存率有所提高，但ICB在很大程度上仍然无效，尤其是在淋巴细胞浸润较差的“冷肿瘤”中。此外，诸如免疫相关不良事件（irAE）等副作用也是ICB临床转化的障碍。最近的研究表明，聚焦超声（FUS）作为一种在临床环境中已被证明对肿瘤治疗有效且安全的非侵入性技术，可以提高ICB的治疗效果，同时减轻潜在的副作用。最重要的是，将FUS应用于对超声敏感的小颗粒，如微泡（MBs）或纳米颗粒（NPs），能够将遗传物质、催化剂和化疗药物精确递送至肿瘤部位并释放，从而增强ICB的抗肿瘤效果，同时将毒性降至最低。在这篇综述中，我们提供了近年来在FUS控制的小分子递送系统辅助ICB治疗方面取得的进展的最新概述。我们强调了不同的FUS增强小分子递送系统对ICB的价值，并描述了这些联合策略的协同效应和潜在机制。此外，我们讨论了当前策略的局限性以及FUS介导的小分子递送系统可能推动实体瘤新型个性化ICB治疗的方式。
