| The development of vaccine adjuvants that are safe,efficient and capable of controlling the dynamic distribution of antigens in cells and the type of immunity is an urgent need for immunotherapy.The polyglutamic acid(PGA)nanoparticles synthesized in this project are biodegradable poly amino acid carrier adjuvants.This project has shown that amphiphilic PGA nanoparticles have high biocompatibility,which can be used as carrier adjuvants to induce related immune responses,and clear TLR-4(Toll-like receptors-4)through the cell surface.The receptor induces its immunological activity and is a very rare carrier adjuvant.This experiment is the first to study a-PGA carrier adjuvant with an alpha helix secondary structure.The results shows that the carrier adjuvant could be efficiently phagocytized by antigen-presenting cells(APC),escape from lysosomes,improve the cross-presenting ability of antigens,and significantly increase the release of TNF-? and the expression of MHC-I molecules,so as to enhanced cellular immunity.In conclusion,nanocarrier based on PGA polymers have potential advantages in developing safe and efficient immunoadjuvant.Considering that a single vaccine adjuvant is difficult to completely kill tumors,this paper designs a PGA nanocarrier system with photothermal-immunological synergistic therapy.The third part designs a PGA nanocarrier system with photothermal-immunotherapy agent.The main scheme of this part is to reduce the potassium permanganate(KMn04)to manganese dioxide(Mn02)by using chicken ovalbumin(OVA),and it's the first time to synthesize the OVA-MnO2(OM)nanoparticles with good photothermal effect.The photothermal conversion efficiency reached 14.91%.Under the near-infrared laser irradiation,about 80%of tumor cells could be killed.Then the OM@PGA-g-F nanoparticles are formed by loading OVA-MnO2 nanoparticles with PGA nanoparticles and the experimental results show that it can play the role of photothermal-immunotherapy. |
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