NIR-Ⅱ small molecule organic probe IR-PEG-FA for intraoperative navigation in hepatocellular carcinoma
Objective To explore the potential of IR-PEG-FA(IPF),a near-infrared two-region(NIR-Ⅱ)small-molecule organic probe,for intraoperative navigation in hepatocellular carcinoma and to perform in vivo near-infrared fluorescence(NIRF)imaging studies and ex vivo and in vivo biosafety assessments.Methods Based on the research of the group,a NIR-Ⅱ small molecule organic probe targeting specific biomarkers of hepatocellular carcinoma was constructed by chemical synthesis.The effects of the nanoprobe on the activities of hepatocellular carcinoma cell lines BEL-7402,HepG-2,HuH-7 and normal hepatocytes HL-7702 were detected by MTT assay;the in vivo biocompatibility of the nanoprobe was evaluated by haemolysis assay,acute toxicity assay and blood biochemistry assay;the in situ hepatocellular carcinoma model was established in mice,and divided into IPF experimental group,IP control group and saline control group.The experimental group was injected with IPF in the tail vein,and the control group was injected with IP and saline in the tail vein,and the specific tumour targeting of their nanoprobe IPF was subsequently detected by using NIR-Ⅱ window imaging;finally,real-time navigational resection of hepatocellular tumours was performed under the NIRF operation window.Results The nanoprobe IPF has no obvious toxicity to BEL-7402,HepG-2,HuH-7 and HL-7702 cells,and the haemolysis rate is below the safety limit of 3%,and it did not cause any significant erythrocyte damage;there is no abnormal behaviour or death of the mice in the acute toxicity test,and there is no obvious effect on the normal structure and function of the important organs(heart,liver,spleen,lungs and kidneys);the liver and kidney functions of mice are all within the normal range.Using IPF nanoprobes for liver tumour cell labelling,the fluorescent signals of hepatocellular carcinoma cells were observed under the NIRF window,and the fluorescent signals in the resected area disappeared after the surgery.Conclusion NIR-Ⅱ small molecule organic probe IPF has good cell safety,excellent biocompatibility,and can efficiently label hepatocellular carcinoma cells,possessing the potential of intraoperative navigation in hepatocellular carcinoma,which provides an idea and a reference for the research related to hepatocellular carcinoma treatment.