Design And Evaluation Of Multi-Component Drug Delivery System Based On Photothermal Therapy

Photothermal therapy is a new type of treatment that uses the photothermal conversion effect to collect energy from the laser and convert it into heat,raise the temperature of the surrounding environment,and ablate the tumor tissue through heat.This is a non-invasive treatment with few side effects,and the radiation parameters and treatment temperature can be precisely adjusted.At the same time,limited by the irradiation range and penetration depth and the low delivery efficiency of photothermal conversion reagents in the tumor,the tumor cannot be completely ablated after photothermal treatment,and it is easy to relapse.The heat resistance and tumor metastasis of the tumor are also faced by photothermal treatment.The serious problem.During photothermal therapy,tumor-associated antigens can be released to stimulate the immune response within the tumor.Therefore,the combination of immunity and photothermal therapy has a good prospect.Targeted therapy drugs have the characteristics of tumor tissue enrichment and low toxic and side effects,can improve the delivery efficiency of photothermal conversion agents in tumors,and show good efficacy in the treatment of highly invasive and metastatic tumors.The main research content of this topic is divided into the following two parts:The first part of the work uses dendritic polyamide-amine(PAMAM)as a gene carrier,and uses thermosensitive phospholipid DPPC and neutrophil membrane as basic materials to construct membrane camouflaged liposome gene delivery nanoparticles encapsulating PAMAM,and characterize membrane camouflaged lipids The particle size,morphology,surface charge and photothermal conversion properties of somatic gene delivery nanoparticles were studied,and their ability to inhibit the expression of IDO 1 protein in mouse melanoma tumor cells and activate BMDC cells was studied.The results of the study show that neutrophil membrane camouflage can enhance the enrichment of liposome nanoparticles in tumor tissues.Compared with single immunotherapy and photothermal therapy,membrane camouflaged liposome gene delivery nanoparticles used in combination therapy are effective Melanoma has a better inhibitory effect.In the second part of the work,a 3D tumor sphere model was constructed to cultivate mouse breast cancer stem cells with CD44+CD24-phenotype,and chitosan nano-drug-loaded particles loaded with gambogic acid were used as drugs to target CD44+tumor stem cells.Tumor stem cells mediated the endocytosis mechanism of chitosan nanodrug-loaded particles,characterized the targeting and killing effect of chitosan nano-drug-loaded particles on CD44+phenotype tumor stem cells in mouse breast cancer tissues,and evaluated the chitosan nano-loaded The ability of drug particles to inhibit tumor metastasis.The results of the study show that chitosan nanoparticles can target the CD44 protein on the surface of cancer stem cells and mediate endocytosis,and at the same time have a stronger ability to inhibit breast cancer metastasis compared with the chemotherapy drug group.