Research On The Design Of Semiconductor Polymer Nanocarriers And Its Application In Tumor Gene Therapy

At present,cancer is one of the main reasons that threaten human health.It is very necessary to develop and apply rapid and effective diagnosis and treatment methods.On the one hand,semiconducting polymer nanoparticles(SPN),as a new class of organic optical nanomaterials,have the advantages of excellent optical properties,good biocompatibility,and easy surface functionalization.They have good performance in biomedicine and other fields.Application potential.On the other hand,RNA interference technology(RNAi)has broad application prospects in the treatment of gene-related diseases,including cancer,and has attracted wide attention from researchers.However,RNA interference technology still faces huge challenges in clinical translation.First,the high negative charge of small interfering RNA(si RNA)molecules makes it difficult for them to pass through cell membranes and physiological barriers,resulting in low intracellular uptake and delivery failure to target cells and tissues.In addition,the instability of si RNA molecules in blood tissue circulation and the extracellular environment is easily affected by nucleases.Therefore,it is very important to develop and research high-efficiency and low-toxicity si RNA delivery vectors.In this thesis,a new type of organic semiconductor polymer nano-gene carrier was constructed and applied to the gene multi-modal therapy of tumor.The main research contents are as follows:1.Semi-Interpenetrating Technique Directed Fabrication of Semiconducting Nanoparticles Construction of Nanogene Vector Construction and Multimodal Gene TherapyIn this chapter,we design and synthesize a three-dimensional network semiconductor polymer nano-gene carrier with a cross-linked structure.Its good hydrophilicity and structural stability make it an excellent carrier.First,through the cross-network structure and the DMAEMA cation on the carrier The electrostatic force with RNA achieves efficient loading of si RNA,and then uses the temperature sensitivity of NIPAM and intracellular p H response to achieve controllable release of gene drugs,uses RNA interference technology to achieve down-regulation of plk1 protein expression,and combines with semiconductor polymer PDPP3 T Excellent light and heat performance,to achieve high efficient killing effect on tumor cells.The research results show that the semiconductor polymer nano gene carriers(PDPP3T NSs)have high gene loading rate,good biocompatibility and tumor targeting.At the same time,using the temperature-sensitive properties of PDPP3 T NSs,the size of PDPP3 T NSs can be transformed after laser irradiation,which promotes endocytosis-mediated tumor penetration,and improves the cell internalization and intracellular release effects of si RNA,which has a significant effect on 4T1 cells The therapeutic effect.The size-transformable semiconductor polymer nano gene carrier has high efficiency gene loading rate and good tumor permeability,and shows great potential in enhancing tumor treatment effects.2.Tumor microenvironment regulation and efficient photothermal therapy based on lactic acid synthesis gene silencing As an important metabolite in the biochemical process,lactic acid is closely related to tumor biological functions such as tumor proliferation,metastasis,angiogenesis and immune escape.In the microenvironment of solid tumors,high-speed aerobic fermentation of glucose by tumor cells leads to increased production of lactic acid,which leads to immune disorders.In this chapter,we use semiconductor polymer nanogene carriers(PDPP3T NSs)as photothermal conversion materials and lactic acid synthesis protein si RNA carriers.By interfering with the synthesis of lactic acid,we can improve the acidic state of the tumor microenvironment and enhance the effect of tumor photothermal therapy.Significantly inhibit the proliferation of tumor cells.The results of the study show that PDPP3 T NSs have good gene loading efficiency,good biocompatibility and tumor targeting,and the targeted knockout genes they carry can inhibit the synthesis of lactic acid and reduce the resistance of tumor cells to photothermal therapy.Ability to improve the effect of photothermal tumor treatment and reduce the temperature required for treatment,further enhancing the effectiveness and safety of photothermal treatment.