Back to Browse Journals » International Journal of Nanomedicine » Volume 7

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

Authors Ma W, Chen M, Kaushal S, McElroy M, Zhang Y, Ozkan C, Bouvet M, Kruse C, Grotjahn D, Ichim T, Minev B

Published Date March 2012 Volume 2012:7 Pages 1475—1487

DOI http://dx.doi.org/10.2147/IJN.S29506

Received 25 December 2011, Accepted 12 January 2012, Published 15 March 2012

Wenxue Ma1, Mingshui Chen1, Sharmeela Kaushal1,2, Michele McElroy1,2, Yu Zhang3, Cengiz Ozkan3, Michael Bouvet1,2, Carol Kruse4, Douglas Grotjahn5, Thomas Ichim6, Boris Minev1,7,8

1Moores Cancer Center, University of California San Diego, 2Department of Surgery, University of California San Diego, 3Laboratory of Biomaterials and Nanotechnology, University of California Riverside, 4UCLA Division of Neurosurgery, Los Angeles, 5Chemistry Department, San Diego State University, San Diego, 6MediStem Inc. San Diego, 7UCSD Division of Neurosurgery, San Diego, 8Genelux Corporation, San Diego, CA, USA

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-γ ELISpot assay (Vector Laboratories, Burlingame, CA). Antigen-specific cytotoxic T lymphocytes (CTLs) were generated and evaluated by CytoTox 96® 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 responses in vivo.

Keywords: peptide delivery, nanotechnology, dendritic cells, vaccination

Download Article [PDF] View Full Text [HTML] 

Creative Commons License This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution - Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php

Readers of this article also read:

Synthesis, characterization, and in vivo efficacy evaluation of PGG–docetaxel conjugate for potential cancer chemotherapy

Yang D, Van S, Shu Y, Liu X, Ge Y, Jiang X, Jin Y, L Yu

International Journal of Nanomedicine 2012, 7:581-589

Published Date: 3 February 2012

Use of DNA microarray analysis in diagnosis of bacterial and fungal endophthalmitis

Sakai T, Kohzaki K, Watanabe A, Tsuneoka H, Shimadzu M

Clinical Ophthalmology 2012, 6:321-326

Published Date: 29 February 2012

Preparation, characterization, and cytotoxicity of CPT/Fe2O3-embedded PLGA ultrafine composite fibers: a synergistic approach to develop promising anticancer material

Amna T, Hassan MS, Nam KT, Bing YY, Barakat NAM , Khil MS, Kim HY

International Journal of Nanomedicine 2012, 7:1659-1670

Published Date: 27 March 2012

Evidence to support the use of vildagliptin monotherapy in the treatment of type 2 diabetes mellitus

Dejager S, Schweizer A, Foley JE

Vascular Health and Risk Management 2012, 8:339-348

Published Date: 18 May 2012

A single-center study evaluating the effect of the controlled adverse environment (CAEsm) model on tear film stability

Abelson R, Lane KJ, Rodriguez J, Johnston P, Angjeli E, Ousler G, Montgomery D

Clinical Ophthalmology 2012, 6:1865-1872

Published Date: 13 November 2012

Efficacy of vildagliptin in combination with insulin in patients with type 2 diabetes and severe renal impairment

Lukashevich V, Schweizer A, Foley JE, Dickinson S, Groop PH, Kothny W

Vascular Health and Risk Management 2013, 9:21-28

Published Date: 23 January 2013

Psychological factors: anxiety, depression, and somatization symptoms in low back pain patients

Bener A, Verjee M, Dafeeah EE, Falah O, Al-Juhaishi T, Schlogl J, Sedeeq A, Khan S

Journal of Pain Research 2013, 6:95-101

Published Date: 4 February 2013

Homozygous familial hypercholesterolemia (HoFH) in Germany: an epidemiological survey

Walzer S, Travers K, Rieder S, Erazo-Fischer E, Matusiewicz D

ClinicoEconomics and Outcomes Research 2013, 5:189-192

Published Date: 3 May 2013