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Nanomedicine ; 22: 102114, 2019 11.
Article in English | MEDLINE | ID: mdl-31655203

ABSTRACT

Plasmid DNA gp100 is able to act as an available vaccine against metastatic melanoma, but its administration is usually limited to parenteral route. Since oral delivery of plasmid DNA is intervened by various physical obstacles, here we constructed a nanogel (Alg-Tat-gp100) with multi-faceted functions through blending-by-blending method. Due to the cooperation of alginate and Tat peptide, Alg-Tat-gp100 demonstrated the significant improvement of stability in the stomach, mucus penetration ability in intestine, and transport across mucus layer and MDCK cells. Moreover, the bone marrow-derived cells were activated with an enhanced co-stimulatory molecule expression. Following immunization using Alg-Tat-gp100 nanogels in C57BL/6 mice, the secretion of IFN-γ and the activation of cytotoxic T cells were significantly improved. Benefiting from those cases, the B16F10 tumor inhibition rate achieved 42.5% by this oral DNA vaccine, suggesting that this multi-faceted nanogel prepared by simple blending-by-blending method may provide a new strategy for oral DNA vaccine delivery.


Subject(s)
Melanoma, Experimental/immunology , Melanoma, Experimental/pathology , Nanogels/chemistry , Plasmids/administration & dosage , Vaccines, DNA/administration & dosage , gp100 Melanoma Antigen/immunology , Administration, Oral , Alginates/chemistry , Animals , Cytokines/metabolism , Dendritic Cells/immunology , Dogs , Female , Immunization , Madin Darby Canine Kidney Cells , Mice, Inbred C57BL , Mucus/metabolism , Neoplasm Metastasis , Permeability , Phenotype , Protein Transport , Spleen/immunology , T-Lymphocytes/immunology , tat Gene Products, Human Immunodeficiency Virus/metabolism , tat Gene Products, Human Immunodeficiency Virus/ultrastructure
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