High-Performance Organic Nano-Optical Therapeutic Reagent Design And Its Anti-Tumor Research

Optical therapy is a new type of thinking in cancer treatment research,and is one of the most popular research fields in biomedical applications.The fundamental reason is that optical therapy has the advantages of high treatment accuracy,small tissue damage and no drug resistance.At present,the common phototherapy reagents mainly have shortcomings such as low absorbance,poor water solubility,easy aggregation,easy quenching fluorescence,and poor dark toxicity.Organic semiconductor nanoparticles are a class of nanomaterials with good biomedical application prospects Its strong light absorption,good light stability,high brightness and good biocompatibility,have been used in the fields of bioimaging,antimicrobial and antitumor therapy,gene and drug delivery in the past decade.This article combines the performance advantages of organic semiconductor nanoparticles and photosensitizers,designed a series of high-performance organic nanometer phototherapy reagents,and initially explored its application in tumor optical therapy.The main research content is divided into the following three aspects(1)High-performance organic-inorganic hybrid photosensitizers are used for tumor photodynamic therapy under the guidance of fluorescence imagingA polyhedral oligomeric silsesquioxane with a three-dimensional cage structure was introduced into the porphyrin structure through a click reaction to synthesize a vinyl-modified POSS-based porphyrin hybrid photosensitizer.At the same time,a novel photosensitizer PorPOSSCl2 modified with dodecyl chain was synthesized by high-efficiency mercapto-alkenyl reaction.By co-precipitating PorPOSSC12 and organic semiconductors(PFO,PFBT),a dual-enhanced nanometer diagnostic probe for fluorescence and photodynamic was prepared.Compared with the commercial photosensitizer THPP,the nanometer diagnostic probe has good colloidal stability,bright fluorescence emission and excellent photodynamic performance,and can be used for tumor photodynamic therapy under the guidance of fluorescence imaging(2)Multifunctional organic semiconductor nanospheres are used in combination therapy of Photothermal/photodynamic/hypoxic activated chemotherapyThe organic semiconductor material PSBTBT was prepared into PSBTBT NPs by reprecipitation method,but a single nanoparticle would quench the fluorescence and photodynamic effect of the photosensitizer Ce6,so PSBTBT NPs were polymerized into PSBTBT NSs.The surface of the multifunctional nanosphere is multifunctional,and the photosensitizer Ce6 is connected through the amide reaction,because the protection effect of the nanosphere on the photosensitizer will not quench the fluorescence and photodynamic effect of Ce6.Reloaded with hypoxia-activated prodrug TPZ,in the tumor microenvironment,the prodrug TPZ will be quickly released in large quantities,and due to the consumption of oxygen during the photodynamic process,it will cause a lack of The situation of oxygen,which in turn activates the anti-tumor chemotherapy activity of the hypoxic prodrug TPZ,has achieved the multi-functional organic semiconductor nanosphere tumor phototherapy and chemotherapy combined treatment performance(3)Organic semiconductor nanoprobes are used for pH/GSH dual-response chemical photothermal combination therapy and intratumoral drug release monitoringA semi-interpenetrating network technology was used to synthesize an organic semiconductor nano-photothermal reagent with a three-dimensional network structure,and the organic semiconductor nano-photothermal reagent was used to load chemotherapy drugs such as DOX.In order to achieve the purpose of monitoring the drug release in the tumor,the fluorescent probe Cy5 is also loaded,and the fluorescence of the fluorescent dye Cy5 is quenched by the excellent fluorescence quenching effect of the organic semiconductor PDPP3T.In the microenvironment of tumors,it was found that the release of DOX and the therapeutic effect can be monitored by the fluorescence recovery of Cy5.The probe also has the role of fluorescence and photoacoustic imaging,and at the same time obtains high-efficiency anti-tumor effects through combined chemical-photothermal therapy.