Cui Rui, Wang Luo, Zhang Dongyun, Zhang Kun, Dou Jianping, Dong Linan, Zhang Yixuan, Wu Jiapeng, Tan Longfei, Yu Jie, Liang Ping
Department of Interventional Ultrasound, PLA General Hospital, Beijing 100853, China.
Department of Medical Ultrasonics, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou 510655, China.
Acta Pharm Sin B. 2022 Sep;12(9):3475-3485. doi: 10.1016/j.apsb.2022.05.026. Epub 2022 May 29.
Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. and experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.
尽管热消融是肝细胞癌（HCC）的常用治疗方法，但热消融不足会留下肿瘤残余物，从而导致复发。据信，这会增加通常发挥促肿瘤作用的M2炎性巨噬细胞。为了解决这个问题，我们设计了d-甘露糖螯合氧化铁纳米颗粒（man-IONPs），以将M2样巨噬细胞极化为抗肿瘤M1表型。实验表明，man-IONPs特异性靶向M2样巨噬细胞，并在微波消融（MWA）不足导致巨噬细胞浸润增加后积聚在消融周边区域。这些纳米颗粒同时诱导促肿瘤的M2巨噬细胞极化为抗肿瘤M1表型，使免疫抑制微环境转变为免疫激活微环境。在一个成熟的原位肝癌小鼠模型中，MWA后巨噬细胞极化对HCC进展产生了强大的抑制作用。因此，将热消融与man-IONPs相结合可以挽救MWA不足后的残余肿瘤。这些结果具有很强的临床转化潜力。
