6533b7d5fe1ef96bd1264863

RESEARCH PRODUCT

Surface Modification of Polysaccharide-Based Nanoparticles with PEG and Dextran and the Effects on Immune Cell Binding and Stimulatory Characteristics.

Peter WichDenise BambergerMatthias KonhäuserDominika HobernikMatthias Bros

subject

Cell typeSurface PropertiesCellPrimary Cell CulturePharmaceutical Science02 engineering and technology010402 general chemistry01 natural sciencesProinflammatory cytokinePolyethylene Glycolschemistry.chemical_compoundMiceImmune systemDrug DiscoveryPEG ratiomedicineAnimalsCells CulturedChemistryMacrophagesCell MembraneDextransDendritic Cells021001 nanoscience & nanotechnology0104 chemical sciencesUp-RegulationMice Inbred C57BLDextranmedicine.anatomical_structureBiochemistryBiophysicsPEGylationMolecular MedicineSurface modificationCytokinesNanoparticles0210 nano-technologySpleen

description

Surface modifications of nanoparticles can alter their physical and biological properties significantly. They effect particle aggregation, circulation times, and cellular uptake. This is particularly critical for the interaction with primary immune cells due to their important role in particle processing. We can show that the introduction of a hydrophilic PEG layer on the surface of the polysaccharide-based nanoparticles prevents unwanted aggregation under physiological conditions and decreases unspecific cell uptake in different primary immune cell types. The opposite effect can be observed with a parallel-performed introduction of a layer of low molecular weight dextran (3.5 and 5 kDa) on the particle surface (DEXylation) that encourages the nanoparticle uptake by antigen-presenting cells like macrophages and dendritic cells. Binding of DEXylated particles to these immune cells results in an upregulation of surface maturation markers and elevated production of proinflammatory cytokines, reflecting cell activation. Hence, DEXylated particles can potentially be used for passive targeting of antigen presenting cells with inherent adjuvant function for future immunotherapeutic applications.

10.1021/acs.molpharmaceut.7b00507https://pubmed.ncbi.nlm.nih.gov/29063757