title: Alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine: effect against breast cancer in mice.
abstract: Legumain-based DNA vaccines have potential to protect against breast cancer. However, the lack of a safe and efficient oral delivery system restricts its clinical application. Here, we constructed alginic acid-coated chitosan nanoparticles (A.C.NPs) as an oral delivery carrier for a legumain DNA vaccine. First, we tested its characteristic in acidic environments in vitro. DNA agarose electrophoresis data show that A.C.NPs protected DNA better from degradation in acidic solution (pH 1.5) than did chitosan nanoparticles (C.NPs). Furthermore, size distribution analysis showed that A.C.NPs tended to aggregate and form micrometer scale complexes in pH<2.7, while dispersing into nanoparticles with an increase in pH. Mice were intragastrically administrated A.C.NPs carrying EGFP plasmids and EGFP expression was detected in the intestinal Peyer's patches. Full-length legumain plasmids were loaded into different delivery carriers, including C.NPs, attenuated Salmonella typhimurium and A.C.NPs. A.C.NPs loaded with empty plasmids served as a control. Oral vaccination was performed in the murine orthotopic 4T1 breast cancer model. Our data indicate that tumor volume was significantly smaller in groups using A.C.NPs or attenuated Salmonella typhimurium as carriers. Furthermore, splenocytes co-cultured them with 4T1 cells pre-stimulated with CoCl2, which influenced the translocation of legumain from cytoplasm to plasma membrane, showed a 4.7 and 2.3 folds increase in active cytotoxic T lymphocytes (CD3(+)/CD8(+)/CD25(+)) when treated with A.C.NPs carriers compared with PBS C.NPs. Our study suggests that C.NPs coated with alginic acid may be a safe and efficient tool for oral delivery of a DNA vaccine. Moreover, a legumain DNA vaccine delivered orally with A.C.NPs can effectively improve autoimmune response and protect against breast cancer in mice.
authors.affiliation: Medical School of Nankai University, Tianjin, China.
authors.forename: Ze
authors.initials: Z
authors.lastname: Liu
authors.forename: Dan
authors.initials: D
authors.lastname: Lv
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
authors.forename: Junbo
authors.initials: J
authors.lastname: Gong
authors.forename: Da
authors.initials: D
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Xiong
authors.forename: Xiaoniao
authors.initials: X
authors.lastname: Chen
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.forename: Xiaoyue
authors.initials: X
authors.lastname: Tan
mesh_terms: D000464:Alginates / Q000737:chemistry*; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001692:Biological Transport; D019496:Cancer Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D048271:Chitosan / Q000737:chemistry*; D003546:Cysteine Endopeptidases / Q000235:genetics* / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D008264:Macrophages / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D010581:Peyer's Patches / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000737:chemistry / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000099240:Asparaginyl Endopeptidase
chemical_list: D000464:Alginates; D019496:Cancer Vaccines; D048271:Chitosan; D003546:Cysteine Endopeptidases; D004337:Drug Carriers; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D019444:Vaccines, DNA; D000099240:Asparaginyl Endopeptidase