PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses

Ma, W, Chen, M, Kaushal, S, McElroy, M, Zhang, Y, Ozkan, C, Bouvet, M, Kruse, C, Grotjahn, D, Ichim, T and Minev, B 2012, 'PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses', International Journal of Nanomedicine, vol. 7, pp. 1475-1487.


Document type: Journal Article
Collection: Journal Articles

Title PLGA nanoparticle-mediated delivery of tumor antigenic peptides elicits effective immune responses
Author(s) Ma, W
Chen, M
Kaushal, S
McElroy, M
Zhang, Y
Ozkan, C
Bouvet, M
Kruse, C
Grotjahn, D
Ichim, T
Minev, B
Year 2012
Journal name International Journal of Nanomedicine
Volume number 7
Start page 1475
End page 1487
Total pages 13
Publisher Dove Medical Press Ltd.(DovePress)
Abstract The peptide vaccine clinical trials encountered limited success because of difficulties associated with stability and delivery, resulting in inefficient antigen presentation and low response rates in patients with cancer. The purpose of this study was to develop a novel delivery approach for tumor antigenic peptides in order to elicit enhanced immune responses using poly(DL-lactide-co-glycolide) nanoparticles (PLGA-NPs) encapsulating tumor antigenic peptides. PLGA-NPs were made using the double emulsion-solvent evaporation method. Artificial antigen-presenting cells were generated by human dendritic cells (DCs) loaded with PLGA-NPs encapsulating tumor antigenic peptide(s). The efficiency of the antigen presentation was measured by interferon-gamma ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96 (R) Non-Radioactive Cytotoxicity Assay (Promega, Fitchburg, WI). The efficiency of the peptide delivery was compared between the methods of emulsification in incomplete Freund's adjuvant and encapsulation in PLGA-NPs. Our results showed that most of the PLGA-NPs were from 150 nm to 500 nm in diameter, and were negatively charged at pH 7.4 with a mean zeta potential of -15.53 +/- 0.71 mV; the PLGA-NPs could be colocalized in human DCs in 30 minutes of incubation. Human DCs loaded with PLGA-NPs encapsulating peptide induced significantly stronger CTL cytotoxicity than those pulsed with free peptide, while human DCs loaded with PLGA-NPs encapsulating a three-peptide cocktail induced a significantly greater CTL response than those encapsulating a two-peptide cocktail. Most importantly, the peptide dose encapsulated in PLGA-NPs was 63 times less than that emulsified in incomplete Freund's adjuvant, but it induced a more powerful CTL response in vivo. These results demonstrate that the delivery of peptides encapsulated in PLGA-NPs is a promising approach to induce effective antitumor CTL
Subject Biomaterials
Keyword(s) Dendritic cells
Nanotechnology
Peptide delivery
Vaccination
DOI - identifier 10.2147/IJN.S29506
Copyright notice © 2012 Ma et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
ISSN 1176-9114
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