Delivery system for the enhanced efficiency of immunostimulatory nucleic acids.
Innate Immun
; 19(1): 53-65, 2013 Feb.
Article
en En
| MEDLINE
| ID: mdl-22732733
ABSTRACT
Toll-like receptors (TLRs) play a key role in the recognition of pathogen-associated molecular patterns, including immunostimulatory nucleic acids (INAs). INAs are recognized by TLRs in endosomes, leading to the activation of signalling pathways that activate the innate immune response. This feature makes INAs and their synthetic analogues useful as adjuvants in vaccines and in cancer treatment. We tested a delivery system for the improvement of the therapeutic effect of INAs which consists of a conjugate between transferrin (Tf) and poly-L-lysine (PLL). Tf is a ligand of the transferrin receptor (TfR) and is internalized via receptor-mediated endocytosis, while PLL binds negatively charged INAs. The TfPLL conjugate protected TLR3 ligand polyinosinicpolycytidylic acid [poly(IC)] from RNase degradation and enhanced the uptake of poly(IC) in HeLa cells. Co-localization between TfPLL-bound poly(IC) and lysosomes demonstrated delivery into the endosomal pathway. Time dependence of the production of IL-6 in the primary cell line showed that TfPLL conjugate enabled a gradual release of poly(IC) and stronger activation of TLR3 receptor in comparison with poly(IC) alone. Only 3 h of stimulation by poly(IC) + TfPLL complexes initiated a strong immune response in contrast to poly(IC) alone. The poly(IC) + TfPLL complexes have potential use for development of advanced vaccine adjuvants and targeted cancer immune therapy in cells that express higher levels of TfR.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polilisina
/
Endosomas
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Transferrina
/
Ácidos Nucleicos
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Sistemas de Liberación de Medicamentos
/
Infecciones
Límite:
Humans
Idioma:
En
Revista:
Innate Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
BACTERIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Eslovenia