Cited by 108Advanced Drug Delivery SystemsNanoparticle-Based Drug DeliveryImmunotherapy and Immune Responses

Alginic acid-coated chitosan nanoparticles loaded with legumain DNA vaccine: effect against breast cancer in mice

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Liu, Ze, Lv, Dan, Liu, Shu, Gong, Junbo, Wang, Da, Xiong, Min, Chen, Xiaoniao, Xiang, Rong +1 more·2013·PLoS ONE

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.

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  1. [25]Borges O, Cordeiro-da-Silva A, Romeijn SG, Amidi M, de Sousa A, et al.. (2006) Uptake studies in rat Peyer’s patches, cytotoxicity and release studies of alginate coated chitosan nanoparticles for mucosal vaccination. J Control Release 114: 348–358. Epub 2006 Jun 2016. 16905219

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Authors
Liu, Z., Lv, D., Liu, S., Gong, J., Wang, D., Xiong, M., Chen, X., Xiang, R., & Tan, X.
Affiliations
  • Nankai University (CN)
  • Tianjin University (CN)
Corresponding author
Tan, Xiaoyue
Venue
PLoS ONE
Published
2013-04-05
Volume
8
Issue
4
Pages
e60190
ISSN
1932-6203 (ISSN-L)
OpenAlex
W1993169857
Cited by
108
References
37
Citations by year
2026: 1 · 2025: 4 · 2024: 2 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 7 · 2018: 9 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 11 · 2013: 7
FWCI
8.02
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Natural Science Foundation of China (81273331, 2013CB967201, 973 Program, 81270774)
  • National Key Research and Development Program of China (2013CB967201)
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
  • Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
legumain, DNA vaccine, breast cancer, chitosan nanoparticles, oral vaccine delivery, attenuated Salmonella typhimurium, 4T1 breast cancer, cytotoxic T lymphocytes, Peyer's patches, nanoparticle aggregation
MeSH terms
Asparaginyl Endopeptidase, Alginates, Animals, Antigen-Presenting Cells, Biological Transport, Cysteine Endopeptidases, Drug Carriers, Female, Gastric Mucosa, Hexuronic Acids, Hydrogen-Ion Concentration, Macrophages, Mammary Neoplasms, Experimental, Mice, Inbred BALB C, Peyer's Patches, T-Lymphocytes, Vaccines, DNA, Cancer Vaccines, Glucuronic Acid, Chitosan, Cell Proliferation, Mice, Nanoparticles

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