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Delivery system for the enhanced efficiency of immunostimulatory nucleic acidsSmole, Anže ...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 polyinosinic:polycytidylic acid [poly(I:C)] from RNase degradation and enhanced the uptake of poly(I:C) in HeLa cells. Co-localization between TfPLL-bound poly(I:C) and lysosomes demonstrated delivery into the endosomal pathway. Time dependence of the production of IL-6in the primary cell line showed that TfPLL conjugate enabled a gradual release of poly(I:C) and stronger activation of TLR3 receptor in comparison with poly(I:C) alone. Only 3 h of stimulation by poly(I:C) + TfPLL complexes initiated a strong immune response in contrast to poly(I:C) alone. The poly(I:C) + TfPLL complexes have potential use for development of advanced vaccine adjuvants and targeted cancer immune therapy in cells that express higher levels of TfRSource: Innate immunity. - ISSN 1753-4259 (Vol. 19, no. 1, 2013, str. 53-65)Type of material - article, component partPublish date - 2013Language - englishCOBISS.SI-ID - 4994842
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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Database name | Field | Year |
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Links to authors' personal bibliographies | Links to information on researchers in the SICRIS system |
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Smole, Anže | 33201 |
Kužnik, Alenka | 29494 |
Oblak, Alja | 29991 |
Pirher, Nina | 26500 |
Jerala, Roman | 06628 |
Source: Personal bibliographies
and: SICRIS
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