Chitosan Microneedle Patch Loaded With Hepatitis B Core Protein Virus-like Particles For Tumor Prevention And Immunotherapy

Melanoma is a malignant disease located on the surface of the skin with high morbidity and mortality.For the treatment of melanoma,clinically,most patients with melanoma in the middle and early stages can be treated by chemotherapy,radiotherapy,or surgery.However,for malignant melanoma,metastasis appears in advanced stages,furthermore,the 5-year survival rate is only about 21%.Therefore,in recent years,the targeting and immunotherapy of melanoma have drawn wide attention.Among them,protein and peptide-based tumor vaccines can be directly chemically modified or genetically engineered to achieve functionalization to induce strong tumor-specific immunity,so it is a promising development direction for tumor prevention and treatment.At the same time,the characteristics of protein and peptide tumor vaccines can be used to modify tumor-associated antigens or neoantigens for the development of personalized tumor vaccines.In addition,the effective delivery of tumor antigens and immunostimulating adjuvants to antigen-presenting cells(APCs)is essential for stimulating the antitumor immune response of melanoma.The skin is rich in APCs cells,which can be used to process and present tumor antigens.Microneedle(MN)is a transdermal delivery manner,which is considered as an attractive transcutaneous immunization method due to their superior piece ability through the stratum corneum and sustained release antigens to the immune-cell-rich dermis/epidermis.Herein,we developed a degradable chitosan-trehalose microneedle patch applied directly to the skin for the prevention and treatment of melanoma.Through the degradation of chitosan microneedles in the skin,the antigen/adjuvant in the microneedles is continuously released,stimulating the uptake of antigen by APCs and presenting them to lymph nodes after cutaneous administration.By conjugating OVA257-264 peptide(OVA),a model antigen,to the surface of hepatitis B core(HBc)protein through genetic engineering method,we designed OVA-HBc protein as a neoantigen to target the B16/OVA melanoma tumor.At the same time,using mesoporous silica nanoparticles(MSN)and CpG oligodeoxynucleotides(CpG ODNs)as a joint adjuvant for vaccines,a noval microneedle patch for melanoma prevention and treatment was developed.As a result,application of MN vaccine containing OVA-HBc protein antigen generated significant specific cytotoxic T lymphocyte(CTL)responses and reshaped the tumor microenvironment(TME).Therefore,the transdermal microneedle tumor vaccine we constructed against melanoma is expected to become a personalized delivery method for the prevention and treatment of melanoma.