The Design,Fabrication,and Application Of Fluorescent Protein Based Sonotheranostics

Early detection,early diagnosis and early treatment have important clinical significance for improving the cure rate and prolonging prognostic survival time of tumor.Drug nanocarrier system integrates the function of tumor in vivo imaging and drug targeted delivery.It can break the time difference between tumor diagnosis and treatment,so as to achieve tumor theranostics.Chemotherapy has the poor targeting and safety of clinical medication,the high toxicity and the multidrug resistance.In addition,a single chemotherapy cannot obtain a good prognostic effect for malignant tumors,and multiple large-dose administration is likely to cause irreversible toxic and side effects.Therefore,it should adopt combined tumor treatment strategies,especially the non-invasive and safe treatment methods.Sonodynamic therapy(SDT)is a non-invasive tumor therapy.Its unique advantages are safety,controllability and good penetrability,which have a better therapeutic effect on deep tumors in situ.However,traditional sonosensitizers has poor water solubility,strong phototoxicity,higher body clearance and lack of tumor specificity.The protein nanocarrier system has better biocompatibility and safety to as a favorable carrier for clinical chemotherapy drugs.We found that SuperNova(SN),a monomer red fluorescent protein,which has ultrasonic response and can be developed as a protein sonosensitizer to integrate fluorescence imaging diagnosis and sonodynamic therapy in vivo.In this study,considering the easy binding of cisplatin with proteins,we used cisplatin,Fe3+,and SN to obtain SNFPs through molecular self assemble,which has higher fluorescence intensity and more stable structure.Through characterizing its physical and chemical properties on the cellular and animal level,it has been systematically proved that SNFPs is a novel multifunctional protein drug nanocarrier platform,which not only achieves fluorescence and MRI dual modality imaging guided drug delivery and controlled release,but also combines chemotherapy and SDT.It can realize that the nanodrug obtains the simplification of the composition but the diversification of function to promot the clinical transformation and application of protein nanocarrier platforms,and provide new ideas for the tumor theranositcs.