Abstract 5705: Orally delivery alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine protect against murine breast cancer

Abstract

Abstract Legumain DNA vaccine has been proven to be a potential treatment approach to protect against breast cancer. However, absence of safe and efficient oral delivery system highly restricts its clinical application. Here, we aim to develop a novel oral delivery system for legumain DNA vaccine with better biocompatibility and efficiency. We constructed alginic acid-coated chitosan NPs (A.C.NPs) and tested its anti-acid characteristics in vitro. DNA agrose electrophoresis data showed that compared to chitosan NPs (C.NPs), A.C.NPs significantly protected DNA from degradation in the condition of pH=1.5. Furthermore, size distribution anlysis showed that when pH<3.0, A.C.NPs aggregated to form the micrometer scale complex and dispersed to nanoparticle sized about 314 nm with the increased pH value. To visualize DNA expression, mice were treated by gavage with the A.C.NPs carrying EGFP expression plasmid. Significant EGFP expression can be detected in the intestinal peryer's patch of mice. Immunoflurescence staining showed that overlapping existed in EGFP and F4/80 (CD11b) positive cells. Full length legumain plasmids were loaded into different delivery systems including chitosan NPs (CL), Salmonella typhi (SL), A.C.NPs (ACL). PBS and A.C.NPs loaded with empty plasmid was also set as control groups (n=5 each group). Oral vaccination was performed in murine orthotropic 4T1 breast cancer model. Animals were scarified when the average tumor size in the PBS group reached 500 mm3. Our data showed that tumor volume was significantly smaller in ACL and SL groups compared to other groups. Further, we isolated splenocytes from mice and co-cultured with 4T1 cells pre-stimulated with hypoxia, which intrigued the translocation of legumain from cytoplasm to membrane. FACS assay showed that active cytotoxic T lymphocytes (CD3+/CD8+/CD25+) in ACL group increased 4.5 folds compared to PBS group and 2.3 folds compared to CL group respectively. Our study suggests that chitosan NPs modified with alginic acid could be a potential safe and efficient tool for oral delivery plasmid DNA. Alginic acid-coated chitosan NPs loaded with legumain DNA vaccine can effectively improve auto-immune response and protect against breast cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5705. doi:1538-7445.AM2012-5705