Orthogonal Reaction-Based Near Infrared Fluorescence Nanoprobe For High Sensitivity Imaging Of Breast Cancer And Imaging-Guided Surgery

Cancer is a severe disease with high mortality rate and threatens human health worldwide.Currently,one of the most effective clinical treatment options for cancer still is surgical resection along with radiotherapy and chemotherapy.However,surgical resection greatly depends on the surgeon's experience to remove cancer,which will inevitably cause some problems,such as small residual tumor?s?due to incomplete resection,resulting in the recurrence of the cancer.Therefore,how to precisely identify tumor and better visualize tumor margins,so that we can eliminate all residual tumor burdens will be key factors for successful tumor surgery.With the development of molecular imaging,imaging-guided precision surgery holds great potential for solid tumors treatment.Among various imaging techniques,near-infrared fluorescence imaging has great advantages in the field of imaging-guided surgery because of its good signal to noise ratio,high sensitivity,simple and convenient instrumentation.A fluorescent probe targeting tumor tissue is particularly critical for near-infrared fluorescence in vivo imaging.The probe should have good targeting capability,strong fluorescence and good biocompatibility.The commonly used near-infrared fluorescent probes are organic small molecule dyes,which have high fluorescence quantum efficiency and good biocompatibility.However,small molecules have rapid metabolism,poor stability,limited enrichment in tumor sites and high background signal,which make it difficult to perform long-term follow-up imaging during the surgery.Therefore,an excellent load carrier is required to deliver and remain as much dye as possible to the tumor site.Nanomaterials have been making a great deal of progress in the diagnosis and treatment of tumors in the past 20 years.In particular,the metabolic environment of tumor is different from normal tissues.Nanomaterials can be permeated and retained in tumor tissues?EPR effect?for a long time.Thus,nanomaterial,which is advantageous for improving the signal-to-noise ratio,is an ideal fluorescent molecular carrier that can be used as imaging probe to realize the long-term follow-up observation and imaging-guided excision surgery of the tumor.In addition,the nanomaterials have large specific surface area,many surface modification sites,and can load more fluorescent molecules to enrich fluorescence molecules.Based on the advantages of nanomaterials and near-infrared imaging,this study designed and synthesized a near-infrared nanoprobe SiO₂-Cy5 and applied it to in vivo imaging and imaging-guided surgery.The results of this study are as follows:1.A silica?SiO₂?carrier with excellent properties was synthesized.The amino group,polyethylene glycol,and orthogonal reaction module TCO were modified on the surface of SiO₂.Then,we obtained SiO₂-TCO which can be used to cancer imaging in vivo.Finally,the dye small molecule Cy5 was modified on the surface of the nanomaterial by orthogonal reaction.The fluorescence probe SiO₂-Cy5 has excellent imaging property,strong stability and good biocompatibility.2.The SiO₂-TCO was used to achieve the in vivo orthogonal reaction two-step imaging of breast cancer.The imaging results were not satisfactory.However,when we do experiments,the imaging results of SiO₂-Cy5 was found to be very nice.Therefore,we decided using SiO₂-Cy5 for in vivo imaging and imaging-guided surgery of breast cancer.3.The near-infrared nano-fluorescence probe SiO₂-Cy5 was used for tumor imaging.Compared with a single dye,its signal intensity at the tumor site was stronger,the signal to noise ratio was improved to 6.8,the imaging effect was better.In addition,the signal can be preserved in the tumor for longer and the boundaries of the tumor can be clearly displayed.This provides a powerful guarantee for long-term follow-up of tumors and lays a foundation for its application to imaging-guided surgery in removing the tumor.4.The near-infrared nano-fluorescence probe SiO₂-Cy5 was used for imaging-guided surgery.Compared to the resection by experienced surgeon,this method can be along the clear boundary of the tumor performing surgery,and reduce the excessive cutting of normal tissue and the surgical wound.In addition,depending on intraoperative imaging can help removing some of the residual tissue that can't be found by naked eye,that is,we can remove the tumor thoroughly in once surgery.