Synthesis And Biological Application Of Peptide Conjugates Of Fluorescein-Derivatives

In recent years,it has become a research hotspot to study the mechanism of tumor development from the aspects of physiological characteristics of cancer cells,signal transduction methods and tumor growth environment factors and further search for new probe targets.Among various probe types,peptide-based molecular beacons,so-called protease-activatable optical probes,have excellent biocompatibility,self-assembly and good chemical modification in protease-targeted drug development,which gives it a promising future.Among them,matrix metalloproteinase MMPs have been proven to play an important role in the transfer and infiltration of tumor cells between tissues due to their ability to hydrolyze extracellular matrices.In view of the wide application prospects of peptide molecular probes for the diagnosis and treatment of tumor cells,this paper designed and synthesized MMP-13 activatable probes with tumor cell targeting function and FRET.The near-infrared fluorescent probe molecule FL-MMP-CY7 was developed by a series of rational design and optimization based on the MMP-13 selective polypeptide,conjugating the side chain of the polypeptide to the two fluorescent dyes FL and CY7 with capable of FRET.At the same time,it also improves the water solubility of FL,which is beneficial to the later photodynamic therapy.The in vitro photophysical properties test verified that our synthesized probes have good FRET effects.In vitro enzymatic experiments and confocal imaging of MDA-MB cells further confirmed that the probe molecule FL-MMP-CY7 can be selectively cleaved by MMP-13,providing conditions for the diagnosis of tumor cells.This simple Smart activation enables real-time monitoring of fluorescein-enhanced fluorescent signals during target protease cleavage and photodynamic therapy with maximum fluorescence signal intensity.The cell viability of the MTT assay showed that the probe after photodynamic therapy was extremely toxic to MDA-MB cells,and the therapeutic efficacy of the probe was achieved.Nanoparticles are emerging technologies in the PDT field that can overcome most of the limitations of traditional PS.Through the peptide self-assembly synthesis of nanoparticles Nano1,the water solubility of the photosensitizer FL was improved,and the targeting and cell uptake were enhanced.Subsequent in vitro experiments also verified that the nanoparticles have excellent photodynamic therapy capabilities.