In vivo delivery of peptides and Toll-like receptor ligands by mannose-functionalized polymeric nanoparticles induces prophylactic and therapeutic anti-tumor immune responses in a melanoma model

We hypothesized that the co-entrapment of melanoma-associated antigens and the Toll-like receptor (TLR) ligands Poly(I:C) and CpG, known to be Th1-immunopotentiators, in mannose-functionalized aliphatic polyester-based nanoparticles (NPs) could be targeted to mannose receptors on antigen-presenting...

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Bibliographic Details
Published in:Journal of controlled release 2015-01, Vol.198, p.91-103
Main Authors: Silva, Joana M., Zupancic, Eva, Vandermeulen, Gaëlle, Oliveira, Vanessa G., Salgado, Ana, Videira, Mafalda, Gaspar, Manuela, Graca, Luis, Préat, Véronique, Florindo, Helena F.
Format: Article
Language:English
Subjects:
Animals
Antigen presenting cells
Cancer vaccine
Cancer Vaccines
Cell Line, Tumor
Cytokines - immunology
Disease Models, Animal
Female
gp100 Melanoma Antigen - administration & dosage
gp100 Melanoma Antigen - chemistry
gp100 Melanoma Antigen - immunology
Granzymes - metabolism
Immunoglobulin G - blood
Ligands
Male
Mannose - chemistry
Mannose receptor targeting
MART-1 Antigen - administration & dosage
MART-1 Antigen - chemistry
MART-1 Antigen - immunology
Melanoma
Melanoma - drug therapy
Melanoma - pathology
Mice, Inbred C57BL
Mice, Transgenic
Nanoparticles
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Oligodeoxyribonucleotides - administration & dosage
Oligodeoxyribonucleotides - chemistry
Ovalbumin - administration & dosage
Ovalbumin - chemistry
Ovalbumin - immunology
Peptides - administration & dosage
Peptides - chemistry
PLGA
Poly I-C - administration & dosage
Poly I-C - chemistry
Polymers - chemistry
TLR
Toll-Like Receptors - immunology
Tumor Burden - drug effects
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Summary:We hypothesized that the co-entrapment of melanoma-associated antigens and the Toll-like receptor (TLR) ligands Poly(I:C) and CpG, known to be Th1-immunopotentiators, in mannose-functionalized aliphatic polyester-based nanoparticles (NPs) could be targeted to mannose receptors on antigen-presenting cells and induce anti-tumor immune responses. High entrapment efficiencies of antigens and immunopotentiators in 150nm NPs were obtained. The co-entrapment of the model antigen ovalbumin and the TLR ligands was crucial to induce high IgG2c/IgG1 ratios and high levels of IFN-γ and IL-2. Mannose-functionalization of NPs potentiated the Th1 immune response. The nanoparticulate vaccines decreased the growth rate of murine B16F10 melanoma tumors in therapeutic and prophylatic settings. The combination of mannose-functionalized NPs containing MHC class I- or class II-restricted melanoma antigens and the TLR ligands induced the highest tumor growth delay. Overall, we demonstrate that the multifunctional properties of NPs in terms of targeting and antigen/adjuvant delivery have high cancer immunotherapeutic potential. [Display omitted]
ISSN:0168-3659
1873-4995
DOI:10.1016/j.jconrel.2014.11.033