Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, PR China; Provincial Clinical and Engineering Center of Digital Medicine, Guangzhou, 510280, PR China.
State Key Laboratory of Molecular Vaccinology and Molecular Diagnosis, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, 361102, PR China.
Cancer Lett. 2021 Jan 1;496:169-178. doi: 10.1016/j.canlet.2020.09.024. Epub 2020 Sep 25.
Nanoparticle-based photothermal ablation (PTA) has been intensively investigated recently. However, the poor biocompatibility of most PTA agents and potential long-term toxicity obstruct their clinical translation. Meanwhile, previous PTA studies are limited to surface tumors because of insufficient light penetration depth of near-infrared (NIR) light for deep abdominal tumors. Therefore, minimally invasive PTA combined with biocompatible agents may pave a promising way to treat deep orthotopic hepatocellular carcinoma (HCC). Herein, a multifunctional agent based on superparamagnetic iron oxide (SPIO) and new indocyanine green (IR820) was constructed with good biocompatibility. Outstanding fluorescence, photoacoustic and magnetic resonance imaging capabilities were observed in vitro. Additionally, in vivo results indicated that early-stage HCC (diameter less than 2 mm) could be effectively detected by this agent. Furthermore, for the first time, we developed minimally invasive laparoscopic-assisted photothermal ablation (L-A PTA) method coupled with this agent to completely ablate orthotopic HCC in nude mice model, neither recurrences nor obvious side effects were observed during the experiments. Remarkable shrinkage of primary tumor and disappearance of intrahepatic metastasis were also observed. In summary, minimally invasive L-A PTA is an effective preoperative neoadjuvant treatment for HCC.
基于纳米颗粒的光热消融（PTA）最近受到了广泛关注。然而，大多数 PTA 试剂的生物相容性差和潜在的长期毒性阻碍了其临床转化。同时，由于近红外（NIR）光的穿透深度不足，以前的 PTA 研究仅限于表面肿瘤，无法用于治疗深部腹部肿瘤。因此，微创 PTA 与生物相容性试剂的结合可能为治疗深部原位肝癌（HCC）开辟一条有前途的途径。在此，构建了一种基于超顺磁性氧化铁（SPIO）和新型吲哚菁绿（IR820）的多功能试剂，具有良好的生物相容性。体外观察到了出色的荧光、光声和磁共振成像能力。此外，体内结果表明，该试剂可有效检测早期 HCC（直径小于 2mm）。此外，我们首次开发了微创腹腔镜辅助光热消融（L-A PTA）方法与该试剂结合，成功地在裸鼠模型中完全消融原位 HCC，实验过程中未观察到复发或明显的副作用。还观察到原发性肿瘤的显著缩小和肝内转移的消失。总之，微创 L-A PTA 是 HCC 的一种有效的术前新辅助治疗方法。
