NIR Fluorescent Molecular Imaging Probes For Accurate Imaging And Surgical Navigation Of Gastric Cancer

Gastric cancer has the clinical characteristics of inconspicuous early symptoms and being prone to metastasize.At the same time,when diagnosed,most of stomach cancers are in the advanced stages,whose five-year survival rate is less than 30%.However,after surgery,the five-year survival rate of patients with early gastric cancer is up to 95%.Therefore,early accurate diagnosis and surgical resection of gastric cancer are the key to reducing the mortality.Nevertheless,Existing clinical detection methods for gastric cancer have low sensitivity,low specificity and high dependence on doctors’experiences,which can easily lead to missed diagnosis of tumors.Near-infrared region(NIR)fluorescence imaging technology has high sensitivity,specificity,safety and low cost.It can realize accurate early imaging of gastric cancer and guide surgeons to completely remove tumors in real time.In this paper,two kinds of NIR fluorescent probes with high specificity and sensitivity were designed based on different innovation points.To evaluate their early diagnosis and surgical navigation in gastric cancer,the animal tumor models were built and used.The specific work was as followed:(1)Click chemical and pre-targeting NIR fluorescent probe for accurate detection and surgical navigation in gastric cancerIn this work,the click chemical molecules TCO and Tz were used to non-destructively label the MG7 antibody and the near-infrared fluorescent dye IRDye800CW,respectively,to obtain MG7-TCO and Tz-IRDye800CW molecules.Then,they were divided into two steps for reaction(MG7-TCO+Tz-IRDye800CW).The first step was to pre-target the MG7-TCO molecules,which binded to MG7-Ab on the surface of gastric cancer cells with high specificity.The second step was to injecte the Tz-IRDye800CW molecules,which highly targeted to the MG7-TCO molecules to mark the gastric cancer.Experimental results showed that compared with the method to label antibody with dye in vitro directly(MG7-TCO-Tz-IRDye800CW),pre-targeting MG7-TCO could avoid steric hindrance and increase antibody targeting efficiency.With the high selection of click chemical reactions,pre-targeting MG7-TCO could increase the fluorescence intensity of the tumor,reduce the background signal,increase the signal-to-noise ratio from 1.9 to 3.7,accurately locate the tumor boundary,and remove a tumor with a diameter of about 2.2mm.(2)pH-responsive NIR fluorescent probe for the diagnosis and treatment integration in gastric cancerIn this work,the near-infrared dye IR780 was mineralized with the calcium phosphate material to form the nanoparticle CaP@IR780.In the microenvironment of the tumor(pH=6.8),it returned to the condition of a single molecule,which could emit fluorescence with the laser irradiation.During the process of the work,compared with Free IR780,the responsive nanoprobe CaP@IR780 had reduced toxicity,increased uptake in the tumor,and weakened background signals.With these good characteristics,it could detect small tumors whose volume is less than 2 mm~3 and achieve precise imaging and surgical navigation of gastric carcinoma in situ and pancreatic metastases.What’s more,IR780 dye has photothermal effect.Based on this,CaP@IR780 finally realized the integration of diagnosis and treatment of gastric cancer.In summary,near-infrared fluorescent probes have good application prospects in early diagnosis and surgical navigation of gastric cancer.At the same time,they have an important role in improving prognosis and increasing survival rate.