A clinical trial of super-stable homogeneous lipiodol-nanoICG formulation-guided precise fluorescent laparoscopic hepatocellular carcinoma resection

Abstract

Background Applying traditional fluorescence navigation technologies in hepatocellular carcinoma is severely restricted by high false-positive rates, variable tumor differentiation, and unstable fluorescence performance. Results In this study, a green, economical and safe nanomedicine formulation technology was developed to construct carrier-free indocyanine green nanoparticles (nanoICG) with a small uniform size and better fluorescent properties without any molecular structure changes compared to the ICG molecule. Subsequently, nanoICG dispersed into lipiodol via a super-stable homogeneous intermixed formulation technology (SHIFT&nanoICG) for transhepatic arterial embolization combined with fluorescent laparoscopic hepatectomy to eliminate the existing shortcomings. A 52-year-old liver cancer patient was recruited for the clinical trial of SHIFT&nanoICG. We demonstrate that SHIFT&nanoICG could accurately identify and mark the lesion with excellent stability, embolism, optical imaging performance, and higher tumor-to-normal tissue ratio, especially in the detection of the microsatellite lesions (0.4 × 0.3 cm), which could not be detected by preoperative imaging, to realize a complete resection of hepatocellular carcinoma under fluorescence laparoscopy in a shorter period (within 2 h) and with less intraoperative blood loss (50 mL). Conclusions This simple and effective strategy integrates the diagnosis and treatment of hepatocellular carcinoma, and thus, it has great potential in various clinical applications.

An exploratory human study of superstable homogeneous lipiodol–indocyanine green formulation for precise surgical navigation in liver cancer

“…Our previous experimental results showed that SHIFT and ICG was sufficiently stable to protect the fluorescence performance of ICG in vitro. More strikingly, SHIFT and ICG could serve as a good embolic agent and may block the tumor progression of VX2 orthotopic hepatocellular carcinoma models 21–23 . This clinical experiment proved that SHIFT and ICG, like traditional lipiodol, had excellent specific tumor deposition in TAE treatment.…”

“…Furthermore, the viscosity of the SHIFT and ICG was comparable to lipiodol and exhibited long-lasting excellent fluorescence navigation in VX2 orthotopic hepatocarcinoma models. 21 To elaborate on the results of the superior performance of SHIFT and ICG previously reported, 22,23 we conducted a clinical application trial. The SHIFT and ICG formulation prepared via SHIFT performs excellent tumor-specific deposition after long-term TAE therapy, which enables ICG to continuously illuminate the tumor regions and microsatellite lesions for specific resection (Figure 1).…”

Recent Advances in Interventional Fluorescence Imaging: Toward the Precise Visualization of Transarterial Mini-Invasive Delivery Systems

“…Our admirable SHIFT nanoICG formulation attracts some surgeon’s attention due to its remarkable and long-time stability and photobleaching resistance of fluorescence and prolonged retention of ICG. A 52-year-old patient with HCC was recruited for the clinical trial of SHIFT nanoICG following ethical approval (Figure a) . After confirming the pathogenetic condition with contrast-enhanced magnetic resonance imaging, SHIFT nanoICG formulation was effectively placed within the primary lesion under the DSA imaging guidance (Figure b).…”

“…(e–i) Blood AST, ALT, T. Bil, Cre, and WBC values before and 12 days after TAE. Reproduced with permission from ref . Copyright 2022, Wiley Periodicals LLC on behalf of American Institute of Chemical Engineers.…”

Present and future of metal nanoparticles in tumor ablation therapy

“…In addition, considering that ablation therapy is an invasive local treatment, intratumoral or peritumoral injection may also be a feasible method for nanoparticle delivery. 110,113 A study by Kettering et al found that after intratumoral injection of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs), most USPIOs remained within the tumor during longterm monitoring, with only a few detected in the liver and spleen, eventually being completely excreted. 199 This indicates that intratumoral injection maximizes the local utilization of nanoparticles.…”