Nanoparticles Targeting Dendritic Cell Surface Molecules Effectively Block T Cell Conjugation and Shift Response

Abstract

Dendritic cells (DCs) are potent professional antigen presenting cells (APC) that activate naïve T cells. Interaction of ICAM-1 and LFA-1 molecules on each cell is required for T cell conjugation to DCs which leads to naïve CD4+ T cell activation and proliferation. Nanoparticles capable of blocking LFA-1/ICAM-1 interaction were studied as inhibitors of T cell conjugation to DCs. Primary DCs were primed with ovalbumin, then treated with a peptide that binds ICAM-1 (LABL), a peptide that binds LFA-1 (cIBR) or the same peptides covalently linked to the surface of poly(dl-lactic-co-glycolic acid) nanoparticles (NPs). LABL-NPs and cIBR-NPs rapidly bound to DCs and inhibited T cell conjugation to DCs to a greater extent than the free peptides, unconjugated nanoparticles (NPs), anti-ICAM-1 antibodies and anti-LFA-1 antibodies. In addition, DCs treated with NPs or with cIBR-NPs stimulated the proliferation of T cells, but DCs treated with LABL-NPs did not stimulate T cell proliferation. Nanoparticles targeting ICAM-1 or LFA-1 also altered cytokine production by DC cocultured with T cells when compared to free ligands suggesting these NPs may offer a unique tool for shaping T cell response.

Prostate-Targeted Biodegradable Nanoparticles Loaded with Androgen Receptor Silencing Constructs Eradicate Xenograft Tumors in Mice

“…The shear associated with these processing conditions requires intensification to create increasingly smaller particle sizes, often damaging plasmid DNA to linear or fragmented forms [35]. In this study, we utilized a solvent diffusion technique that reduced shear and improved retention of DNA structure [36–38]. Phenol/chloroform extraction assay revealed that PSMA aptamers were successfully conjugated onto the surface of the PLGA NPs (Figure 3B).…”

“…Our previous work illustrated the advantages of monodisperse particles in controlling the release kinetics of drugs from the polymer matrix [36–38]. Our recent studies also indicated that particle size can be optimized for different delivery purposes and plasmid DNA constructs can be encapsulated without any damage [43].…”

Single-step grafting of aminooxy-peptides to hyaluronan: A simple approach to multifunctional therapeutics for experimental autoimmune encephalomyelitis

“…LABL is a peptide that inhibits the binding of intracellular cell-adhesion molecule-1 (ICAM-1) [32]. This peptide was also shown to interfere with immune cell adhesion in immortalized and primary cell culture models [33-35]. Coincident delivery of antigen and LABL, therefore, may inhibit the inflammatory immune response and provide ‘antigen-specific’ therapy for treating autoimmune diseases.…”

Autoimmune Therapies Targeting Costimulation and Emerging Trends in Multivalent Therapeutics

“…In vitro studies of co-cultures of DCs with T cells showed that nanoparticles targeting ICAM-1 or LFA-1 were significantly better inhibitors of synapse formation compared with similar concentrations of free ligands [164]. Furthermore, the targeted nanoparticles drammatically shifted the response of these cells as evidenced by a significant shift in cytokine expression profiles and T-cell proliferation.…”