Design Of Semiconductor Polymer Nanocarriers And Its Application In Long-term Gene Therapy And Low-temperature Photothermal Therapy

At present,cancer is one of the major diseases that threaten human health.With the continuous development of science and technology,the innovation of cancer treatment methods and the improvement of treatment effect have become the main direction of current research.Traditional treatment methods such as surgical treatment,radiation therapy and chemotherapy all have drawbacks,such as toxic and side effects on normal tissues,easy recurrence and poor treatment.Gene therapy have attracted enormous interest due to its good targeting,low side effects and non-cytotoxicity.Gene therapy is the delivery of genetic material to cells through specific nanocarriers to treat diseases by closing genes that produce defective proteins or introducing genes that produce beneficial proteins.The key to gene therapy is to design a gene delivery system that can efficiently deliver target nucleic acids to tumor cells.In this work,two multifunctional gene delivery systems based on semiconductor nanopolymers were designed and developed to achieve efficient delivery and release of si RNA and pDNA,and regulate the expression of related target proteins at the gene level to achieve long-term gene therapy and low-temperature photothermal therapy.The research contents are as follows:1.Long-term gene therapy based on charge-reversal semiconductor polymer nanocarriersIn this chapter,we designed and successfully prepared a multifunctional gene delivery system based on semiconductor nanopolymers PDPP3T-BDEAEA@NSs.Plasmid DNA were loaded on PDPP3T-BDEAEA@NSs by electrostatic adsorption between BDEAEA cations and plasmid DNA.The temperature-sensitive characteristics of NIPAM and intracellular reactive oxygen species(ROS)response of BDEAEA were used to achieve the controllable release of plasmid DNA.Plasmid DNA will participate in transcription and translation in the nucleus to regulate the expression of interleukin2(IL-2)protein.After that,the nano-gene vector PDPP3T-BDEAEA@NSs will bind interleukin 2(IL-2)protein through electrostatic interaction to achieve long retention of interleukin 2(IL-2)protein in the cell,which is a long-term gene therapy method.The results show that PDPP3T-BDEAEA@NSs have stable structure,good morphology,uniform sized,and good plasmid DNA loading effect and photothermal performance.PDPP3T-BDEAEA@NSs-pDNA effectively improves the delivery efficiency of pDNA,and effectively enhances the expression of IL-2 protein in cancer cells.PDPP3TBDEAEA@NSs also have good biocompatibility,which indicates the semiconductor nanopolymer gene carrier with reversible surface charge has high gene loading efficiency and gene delivery effect,and is a very promising gene delivery carrier.2.Tumor microenvironment p H regulation and low temperature photothermal therapy based on semiconductor polymer nano-gene carrierIn this chapter,we designed and successfully prepared a multifunctional gene delivery system based on semiconductor nanopolymers(PDPP3T-DMAEMA@NSs).After quaternary ammonium salt treatment,the surface of the nanocarrier carries positive charge.Negatively charged si RNA are loaded into PDPP3T-DMAEMA@NSs through electrostatic adsorption of the cationic quaternary ammonium group.The p H and GSH(glutathione)responsive characteristics of the material are used to achieve controlled release of si RNA.si RNA can target lactate dehydrogenase(LDHA)gene.While achieving intracellular delivery of si RNA,PDPP3T-DMAEMA@NSs can also protect si RNA from nuclease degradation and premature removal.The results show that PDPP3T-DMAEMA@NSs have stable structure,good morphology,uniform dispersion,good biocompatibility and good si RNA loading effect and photothermal performance.PDPP3T-DMAEMA@NSs-si RNA can achieve effective intracellular delivery of si RNA,and can efficiently release si RNA in response to the tumor cell microenvironment in the cell.si RNA can effectively regulate the expression of lactate dehydrogenase(LDHA),thereby affecting the glycolysis process of tumor cells,reducing the content of lactic acid in the cell microenvironment,and increasing the p H value of the tumor cell microenvironment.The neutral cell microenvironment p H value will improve the photothermal treatment effect,achieve low-temperature photothermal treatment and effectively kill tumor cells at lower temperatures.Therefore,the semiconductor nanopolymer gene carrier offers high gene loading and delivery,and in combination with its photothermal properties,achieves the synergistic effect of low temperature photothermal therapy and gene therapy...