The Application Of Nanoprobes And Drug-loading Platforms Based On Au-Se Bonds In The Diagnosis And Treatment Of Breast Cancer

Breast cancer is one of the major malignant tumors threatening women Well-being at present.Distant metastases were found about 25 to 40 % of breast cancer patients,which is often the main reason for treatment failure.Therefore,it is a great challenge to diagnosis and treat breast cancer for current public health.Some research show that the communication mechanism involved in signal molecules play an important role in the occurrence,development,metastasis and recurrence of breast cancer.Consequently,real-time monitoring the signal molecules and revealing their relationships have great significance for differential diagnosis and prognosis of breast cancer.At present,the clinical treatment of breast cancer mainly includes surgical treatment,radiation therapy,chemotherapy and endocrine therapy.The problems of the lack of targeting ability,the potential side effects and the drug resistance are common in these treatment methods,so the efficacy is not satisfactory.In recent years,with the development of nanotechnology,the nano-drug carriers have been widely applied in the fields of diagnosis,imaging and treatment of cancer cells.Gold nanoparticles(Au NPs)are commonly used in the construction of functional nanoprobes because of their easy surface modification,good fluorescence quenching performance and unique bioaffinity.Mesoporous silica nanoparticles(MSNs)have the characteristics of high surface area,large pore volume,adjustable mesoporous pore size,good biocompatibility and easy functionalization,so there are considered to be ideal drug delivery carriers.In this study,the recent research progress and development trends of gold nanoprobes and stimuli-responsive drug delivery systems in cancer diagnosis and treatment are reviewed.Based on the above,we carried out the following work:1.We designed a Au-Se-based nanoprobe for simultaneously imaging the invasion markers uPA and MMP-2 and real-time in situ monitoring their changes in living cells.The gold nanoprobe was assembled by coupling Rhodamine B(RhB)-modified peptide and fluorescein isothiocyanate(FITC)-modified peptide onto the gold nanoparticle’s surface via Au-Se bond.The peptide chains labeled with RhB present an excitation/emission wavelengths of 561/583 nm,while the peptide chains labeled with FITC retain an excitation/emission wavelengths of490/520 nm,so it should be no overlap to avoid cross interference between the two fluorescence signals.Upon meeting uPA and MMP-2,the peptide chains labeled with RhBcould be specifically cleaved by uPA,and the peptide chains labeled with FITC could be specifically cleaved by MMP-2,triggering fluorescence recovery of the dyes.The experiment results indicated that the nanoprobe possessed better prevention of glutathione interference compared to the conventional Au-S nanoprobe,which made it better applied to reflect the invasion ability of different breast cancer cells.Furthermore,the Au-Se nanoprobe was also used to visually confirm that the upstream uPA can activate the downstream MMP-2.Thus,our work offered a visual biomarker detection method for judgment of breast cancer malignancy degree,and also provided an effective strategy to investigate the relationships between signal molecules of other signaling pathway in the future.2.We designed a gold nanoparticle(AuNP)-capped mesoporous silica nanoplatform for the detection of uPA and targeted treatment of breast cancer.We assembled the gold nanoprobe by coupling Rhodamine B(RhB)-modified peptide onto the gold nanoparticle’s surface via AuSe bond,and simultaneously used as a capping of MSN pores to prevent the premature release of the load.Upon meeting uPA,the peptide chains labeled with RhB could be specifically cleaved by uPA,triggering fluorescence recovery of the dye and the release of resveratrol.The experiment results show that the drug-loading platform has strong resistance to biothiols in complex biological systems and can release drugs accurately.The nano-platform could effectively solve the problem of the premature release of the load,and avoid damage to normal tissues and cells,and improve the therapeutic effect of tumor in mouse.