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J Control Release. 2015 Jan 28;198:91-103. doi: 10.1016/j.jconrel.2014.11.033. Epub 2014 Dec 5.

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.

Author information

1
Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal; Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, 1200 Brussels, Belgium.
2
Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal.
3
Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, 1200 Brussels, Belgium.
4
Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, 1649-025 Lisbon, Portugal.
5
Louvain Drug Research Institute, Advanced Drug Delivery & Biomaterials, Université Catholique de Louvain, 1200 Brussels, Belgium. Electronic address: veronique.preat@uclouvain.be.
6
Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, 1649-003 Lisbon, Portugal. Electronic address: hflorindo@ff.ul.pt.

Abstract

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.

KEYWORDS:

Antigen presenting cells; Cancer vaccine; Mannose receptor targeting; Melanoma; Nanoparticles; PLGA; TLR

PMID:
25483429
DOI:
10.1016/j.jconrel.2014.11.033
[Indexed for MEDLINE]

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