Minimally invasive photothermal ablation assisted by laparoscopy as an effective preoperative neoadjuvant treatment for orthotopic hepatocellular carcinoma

Abstract

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.