Nano-vesicles based on phospholipid-like amphiphilic polyphosphazenes to orally deliver ovalbumin antigen for evoking anti-tumor immune response.
Aimed at evoking an adequate anti-tumor immune response via oral administration route, this study constructed functionally and structurally mimicking-bacteria-membrane (MBM) nano-vesicle (RGD-PEOP) to orally deliver ovalbumin (OVA) antigen. In terms of simulating bacterial membrane structure, we creatively designed this nano-vesicle to have phospholipid-like octadecylphosphoethanolamine groups in vesicle membrane to improve OVA loading by means of specific interactions including salt bridge and hydrogen bond interaction. For simulating bacterial membrane function, the RGD peptide was modified onto the nano-vesicle surface, and the resulting vector displayed a good transport ability with a 3.4-fold higher than free OVA. In vitro and in vivo assay showed that the expression of co-stimulatory molecules and MHC class II complexes was significantly enhanced by MBM nano-vesicle. IFN-γ and IL-4 levels also increased several folds in the MBM nano-vesicle group. Consequently, MBM nano-vesicle achieved the highest in vivo inhibition rate of 69% against E.G7-OVA tumors among all the oral groups. These results suggest that this MBM nano-vesicle may be a promising vector to orally deliver OVA antigen for cancer immunotherapy. STATEMENT OF SIGNIFICANCE: Developing an effective non-bacterial carrier for oral cancer immunotherapy remains challenging. This work constructed a mimicking-bacteria-membrane nano-vesicle based on phospholipid-like amphiphilic polyphosphazenes for oral delivery of ovalbumin antigen. With the considerable capability to load ovalbumin antigen and target M cells, the nano-vesicle produced remarkable tumor suppression in vivo by evoking anti-tumor immune response.
['Shen|Yurun|Y|', 'Hu|Yumiao|Y|', 'Qiu|Liyan|L|']
D000284:Administration, Oral D000818:Animals D000970:Antineoplastic Agents D015496:CD4-Positive T-Lymphocytes D018414:CD8-Positive T-Lymphocytes D045744:Cell Line, Tumor D004337:Drug Carriers D005260:Female D007167:Immunotherapy D008081:Liposomes D008807:Mice, Inbred BALB C D009369:Neoplasms D009943:Organophosphorus Compounds D010047:Ovalbumin D011108:Polymers D013501:Surface-Active Agents
Nano-vesicle Polyphosphazene Ovalbumin Anti-tumor immune response Oral delivery