Construction Of Vaccine Delivery Systems And Their Application In Cancer Immunotherapy

With the development of society and the continuous advancement of technology,the development of vaccines is not only used for traditional disease prevention,but also expected to be an effective method for disease treatment(such as anti-tumor).Immunization of tumor vaccine is an important tumor immunotherapy,which could activate immune system to treat turmor.Tumor antigens include tumor cells,DNA sequences of tumor antigens,tumor-associated proteins or peptides,which generally have a low antigen immunogenicity and cannot induce effective antigen-specific cellular immune response while used alone.Therefore,it is necessary to find a suitable vaccine delivery system to assist tumor antigens to achieve effective tumor immunotherapy effects.In this study,we studied the effect of several nanomaterials as a vaccine delivery system on enhance immunogenicity of antigens and/or change antigen-specific immune response type.In addition,we studied their effects on immune anti-tumor.The key to preventing/treating a disease by vaccination is to induce antigen-specific cellular immune responses.Then,it is most important to deliver a sufficient amount of antigen to the antigen-presenting cells(APCs).Phosphocholine(PC)group is the hydrophilic head of the phospholipid bilayer of cell membrane,therefore,its orientation group choline phosphate(CP)could be synthesized,which could interact with PC group by electrostatic interaction.Thus,the CP group could be a functional molecule to modify nanomaterials using for drug or vaccine delivery.In this study,we investigated whether the nanomaterial poly(choline phosphate-L-glutamic acid)(p CPGlu)and nhexadecylcholine phosphate(C16-CP)that with strong cell membrane adhesion ability could be vaccine delivery systems to enhance the level of antigen-specific immune responses and the effect of cancer immunotherapy.The results showed that the nanomaterials of p CPGlu and C16-CP can be vaccine delivery systems to elicit a rapid uptake and efficient presentation of antigen by APCs,following with strong antigenspecific cellular and humoral immune responses,which would be suitable vaccine delivery systems to deliver tumor antigens for cancer immunotherapy.Due to the complex mechanism of tumor immune,diverse tumor antigens,large differences among individual patients and immune monitoring escape ability of tumor,it is difficult to get effective clinical treatment by immunotherapy alone.In recent years,the photothermal therapy(PTT)has been used as a new method for cancer therapy,which was also combined with other methods(such as chemotherapy,photodynamic therapy and immunotherapy)for cancer therapy.In this study,we designed and prepared black phosphorus-based two-dimensional nanosheet materials(BP@HPAA/Cp G),Which consisted of black phosphorus(BP),hyperbranched polyamidoamine(HPAA),and Cp G.BP is a novel two-dimensional nanomaterial with high photothermal conversional efficiency,which was usually used for drug/gene delivery because of its high loading ratio.Hyperbranched polyamidoamine(HPAA)is a redox-responsive polycationic nanomaterial were usually constituted smart nanoparticles for cancer treatment.Cp G is a potent Toll-like receptor(TLR)9 agonist,which can enhance the strength of immune responses.Therefore,we combined nanoparticles BP@HPAA/Cp G with checkpoint blockade(anti-CTLA4)for cancer photothermal/immunotherapy.The results demonstrated that the combination of photothermal therapy and immunotherapy can effectively eliminate the tumor in situ,and also can induce a strong immune response and immune memory to inhibit tumor metastasis and recurrence.