Construction And Performance Study Of Tumor Microenvironment-responsive Nano-photosensitizer

Nanocarriers have prominent advantages over traditional methods of cancer diagnosis and treatment due to their small size,strong targeting and small toxicity.In order to combine the diagnosis and treatment of cancer and improve the release efficiency of nanocarriers at tumor targets,a nanometer photosensitizer with function of diagnosis and treatment was designed in response to tumor reduction microenvironment.First we synthesized PSMA-SS-TPS,a polymer with GSH response effect.It was mixed with ZnPc,a photosensitizer with photodynamic therapeutic effect.Then a GSH responsive nano-photosensitizer with diagnostic and therapeutic functions was prepared by co-precipitation injection method.The properties of the nano-photosensitizer were characterized.Then it was applied to the cellular level and the good effect of diagnosis and treatment was obtained.The main work contents are as follows:1.The polymer PSMA-SS-TPS was synthesized in three steps.Then,we use absorption spectroscopy,emission spectroscopy,Fourier infrared spectroscopy,hydrogen nuclear magnetic resonance spectroscopy and mass spectrometry to analyze and characterize the products of each step and prove that the polymer had been prepared.2.The disulfide bond(S-S)of PSMA-SS-TPS can be reduced and broken by GSH,and the broken bond led to the release of the fluorescent molecule TPS which can induced the Aggregation-Induced Emission(AIE).The response of polymer PSMA-SS-TPS to GSH was verified in organic solvent THF,deionized water and PBS respectively.It was found that in PBS which is close to the cell environment,its fluorescence intensity increased by 1.4 times after adding GSH 8 min,indicating that it had a good GSH response effect.Then nanoparticles with function of cancer diagnosis and treatment were prepared by coprecipitation injection method.The nanoparticles were optimized by adjusting the dosage ratio of photosensitizer ZnPc,and the optimal composition of nano-photosensitizer was obtained as ZnPc:PS-PEG-COOH:PSMA-SS-TPS=4:10:86 through the photodynamic treatment effect and GSH response test.Subsequently,the nano-photosensitizers were characterized by DLS,TEM and Zeta potential,respectively.It was found that the nano-photosensitizers were spherical shape with uniform morphology.The particle size was about 50 nm and the surface was negatively charged.3.With breast cancer MCF-7 cells as the experimental subjects,the dark toxicity test proved that the nano-photosensitizers were non-toxic to cells when the concentration was less than 182 ?g/mL.The phototoxicity test and confocal imaging showed that the nano-photosensitizers were easy to be engulfed by tumor cells and had good GSH response effect.They could be used for fluorescence imaging and photodynamic therapy of tumor cells.