Targeting Nanoprobes Based On IGF-1R For Precise Photothermal Therapy Of Pancreatic Cancer Guided By Optical Imaging

BackgroundPancreatic cancer is one of the most lethal malignancies worldwide.Traditional imaging diagnostic methods are generally lacking in specificity,and they are difficult to diagnose lesions lacking typical imaging features.Their diagnostic rate for pancreatic cancer is not high.Furthermore,the effective surgical resection rate of pancreatic cancer is much lower than 20%.For most pancreatic cancer patients who have lost their chance of surgery,the current treatment options are unsatisfactory.Therefore,there is an urgent need to find more effective diagnosis methods atnd anti-cancer strategies for pancreatic cancer.Molecular imaging technology has attracted great attention because of its good achievements in tumor diagnosis and treatment.In this study,a nanoprobe which integrates with diagnostics and treatment was designed to combine preoperative imaging,intraoperative navigation and photothermal therapy to explore new strategies for diagnosis and treatment of pancreatic cancer.ObjectiveThe near-infrared fluorescent nanoprobes capable of actively targeting pancreatic cancer were designed for molecular imaging and photothermal therapy of pancreatic cancer,thereby exploring the the application of nanoprobes for diagnosis and treatment in pancreatic cancer.Methods1.Experiments on nanoprobes:Single-walled carbon nanotubes were subjected to a series of chemical and biological modifications,and their physical and chemical properties were characterized after purification.2.Experiments on cells:Investigating the cytotoxicity and photothermal toxicity of nanoprobes.Detecting the expression of specific targets in pancreatic cancer cells,and the targeting performance of nanoprobes in pancreatic cancer cells.3.Experiments on animals:Various molecular imaging techniques were used to observe the distribution and metabolism of nanoprobes in tumor-bearing mice.The near-infrared fluorescence imaging was used to accurately locate the tumor area and its boundary,and visualized photothermal therapy and efficacy observation were performed.The relevant tissues were taken for staining observation.Results1.Experiments on nanoprobes:The near-infrared fluorescent nanoprobes with pancreatic cancer targeting ability had been successfully surface-modified.They had a negative potential,long tubular structure,good light absorption characteristics and light-emitting characteristics.Their photothermal conversion efficiency were promising,with excellent solution stability,zeta potential stability,serum stability and photothermal stability.2.Experiments on cells:The nanoprobes had low cytotoxicity within the detection range,and the photothermal toxicity was obvious.The specific targets had a higher expression rate on the BXPC-3 and PANC-1 pancreatic cancer cell lines.The nanoprobes that coupled with targeting antibodies showed significant cells targeting performance.3.Experiments on animals:Whether optical imaging or photoacoustic imaging,it could be observed that the nanoprobes mainly accumulate in the tumor area.While inside the tumor,the nanoprobes were distributed around the disordered tumor blood vessels.After the targeting nanoprobes entered the body,the tumor was identified by optical imaging and photothermal therapy was performed at a temperature of about 48.53 0C,and caused obvious apoptosis and necrosis.The median survival time of this targeting nanoprobes group of tumor-bearing mice was about 2.5 times that of the control group.No significant cells damages were observed in important organs of all groups.ConclusionThe designed nanoprobes had many excellent properties and could diagnose pancreatic cancer by optical-photoacoustic dual-modality imaging.The near-infrared fluorescence imaging was used to identify the tumor area and its boundary in real time,and then the tumor suppressing effect was carried out by precise photothermal therapy,thereby achieving the integration of diagnosis and treatment.