Surface assembly of poly(I:C) on PEGylated microspheres to shield from adverse interactions with fibroblasts

Journal of Controlled Release : Official Journal of the Controlled Release Society
Annina M HafnerHans P Merkle

Abstract

By expressing an array of pattern recognition receptors (PRRs), fibroblasts play an important role in stimulating and modulating the response of the innate immune system. The TLR3 ligand polyriboinosinic acid-polyribocytidylic acid, poly(I:C), a mimic of viral dsRNA, is a vaccine adjuvant candidate to activate professional antigen presenting cells (APCs). However, owing to its ligation with extracellular TLR3 on fibroblasts, subcutaneously administered poly(I:C) bears danger towards autoimmunity. It is thus in the interest of its clinical safety to deliver poly(I:C) in such a way that its activation of professional APCs is as efficacious as possible, whereas its interference with non-immune cells such as fibroblasts is controlled or even avoided. Complementary to our previous work with monocyte-derived dendritic cells (MoDCs), here we sought to control the delivery of poly(I:C) surface-assembled on microspheres to human foreskin fibroblasts (HFFs). Negatively charged polystyrene (PS) microspheres were equipped with a poly(ethylene glycol) (PEG) corona through electrostatically driven coatings with a series of polycationic poly(L-lysine)-graft-poly(ethylene glycol) copolymers, PLL-g-PEG, of varying grafting ratios g from 2.2 up ...Continue Reading

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Citations

Jun 12, 2013·Advanced Drug Delivery Reviews·Annina M HafnerHans P Merkle
Mar 7, 2013·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Ying Waeckerle-MenPål Johansen
Jul 3, 2013·Biochimica Et Biophysica Acta·Boon M TeoBrigitte Städler
Aug 23, 2019·Biomedit︠s︡inskai︠a︡ khimii︠a︡·E D DanilenkoG M Sysoeva
Jan 1, 2019·Biochemistry (Moscow) Supplement. Series B, Biomedical Chemistry·E D DanilenkoG M Sysoeva

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