Intelligently-responsive Vaccine Delivery Systems Used For Anti-tumor Immunotherapy

Tumors are one of the major diseases that severely threaten human health.The existing clinical treatment methods are mainly surgery,radiotherapy and chemotherapy.In recent years,the rapidly emerging and developing tumor immunotherapy is a newly treatment for eliminating cancer cells by using the body's own immune system,which is becoming the fourth largest cancer treatment.Compared with traditional therapy,immunotherapy is the most promising advanced cancer treatment strategy,which effectively coordinates the autoimmune system to target and eradicate tumor cells,causing long-lasting anti-tumor effects in vivo and inhibiting the migration and recurrence of tumor cells.The common method of tumor immunotherapy is to immunize tumor antigens to trigger an antigen-specific immune response to kill tumor cells.The utility of functional nanomaterials as tumor antigen delivery vehicles can significantly improve antigen delivery efficiency and further enhance antigen-specific immune responses.During the development of tumor vaccines,the use of intelligent antigen delivery systems with the excellent properties of inducing strong cellular immunity to enhance the killing effect on tumor cells is one of the important research hotspots of tumor immunotherapy.1.Redox-responsive fluorinated poly(amidoamine)as a vaccine delivery system for anti-tumor immunotherapyAs a potential method for tumor therapy,widespread attention has been paid to the design of safe and effective nano-vaccine vectors to induce efficient antigen cross-presentation and cellular immune responses.Foreign antigenic proteins are delivered to the cytoplasm of antigen presenting cells(APCs)to induce a strong cellular immune response through antigen cross presentation.Herein,we used a heptafluorobutyric anhydride fluorination modified redox-responsive hyperbranched macromolecular poly amide(HPAA)to prepare a fluoride poly(amide amine)(HPAA-F7).The unique advantages of HPAA as a vaccine vector are combined with the fluoridation strategy in gene carriers to construct a vaccine delivery system for anti-tumor therapy.The immunization results indicated that HPAA-F7 as a vaccine carrier is beneficial to promote intracellular uptake and cytoplasmic delivery of antigenic proteins and induce effective anti-tumor cellular immunity.2.pH/reduction dual responsive metal-polyphenol network structure as a vaccine vector for anti-cancer immunotherapyAlkaline MgO nanoparticles were utilized as the carrier for co-loading model antigen ovalbumin(OVA)and adjuvant(CpG),and then the antigen complexes are coated by pH and reduction dual-sensitive and PEG modified metal-phenolic networks for anti-cancer immunotherapy.The vitro release tests demonstrate that the antigen delivery system with pH/reduction dual sensitivity successfully promotes OVA to enter into cytosol and crosspresentation.Results of in vivo dendritic cells(DCs)activation and CTLs response experiments further indicate that the delivery system facilitates the antigen presentation via MHC-I pathway and enhances the cellular immune response.The excitation of effector memory T cells tests demonstrate that the delivery system indeed triggers immune memory effect,which can availably prevents recurrence and migration of tumor cells.