Intraoperative Identification of Liver Cancer Microfoci Using a Targeted Near-Infrared Fluorescent Probe for Imaging-Guided Surgery

Abstract

Difficulties in the highly sensitive detection of tumour microfoci represent a critical obstacle toward improved surgical intervention in liver cancer. Conventional preoperative imaging methods and surgeons’ subjective experience are limited by their inability to effectively detect tumour lesions measuring less than 2 mm; however, intraoperative fluorescence molecular imaging may overcome this limitation. Here, we synthesised an arginine-glycine-aspartic acid (RGD)-conjugated mesoporous silica nanoparticle (MSN) highly loaded with indocyanine green (ICG) dye that could accurately delineate liver cancer margins and provide excellent tumour-to-normal tissue contrast intraoperatively. The increased ICG loading capacity and tumour specificity enabled the identification of residual microtumours and satellite lesions measuring less than 1 mm in living mice. Histological analysis validated the sensitivity and accuracy of this approach. We believe this technique utilising a new fluorescent nanoprobe with intraoperative optical imaging may offer a more sensitive and accurate method for liver cancer resection guidance, resulting in better surgical outcomes.

Recent progress in biomedical applications of RGD‐based ligand: From precise cancer theranostics to biomaterial engineering: A systematic review

“…Fluorescent labeling (FITC) and fluorescent microscope were used to investigate the ability of free peptide connecting to the same receptor (Oyama et al, 2003). Cyclic-RGD which binds specifically to liver cancer, was another probe employed by Zeng et al in 2016 to provide a detection system for liver cancer cells using mesoporous silica nanoparticle (MSN) along with indocyanine green (ICG) dye. As this system applied a fluorescent probe combining with intraoperative optical imaging, the surgical outcomes can improve significantly .…”

Identification of a Glypican‐3‐Binding Peptide for In Vivo Non‐Invasive Human Hepatocellular Carcinoma Detection

“…However, due to the high molecular weight and long circulation time in vivo, the detection of HCC with GPC3 antibody probes is slow. Phage display technology, a highly efficient tool to identify small peptides with affinity to a target, has been investigated in recent years for use in the clinical diagnosis and treatment of various types of cancers . Hence, the discovery of peptides functionally targeting HCC cells has received great attention as a target of imaging diagnostic methods and to be applied as a potent target therapy.…”

Combination of Fluorescence-Guided Surgery With Photodynamic Therapy for the Treatment of Cancer

“…A group synthesized arginine–glycine–aspartic acid (RGD)-conjugated ICG mesoporous silica nanoparticles as an intraoperative fluorescent probe and used the probe to test selectivity. 92 The results showed that this novel probe led a significantly enhanced optical signal in hepatic tumor lesions, provided remarkable optical contrast at the liver tumor margin, and displayed a high potential for the detection of residual microtumors.…”