Polyester Nanoparticles Presenting Mannose Residues: Toward the Development of New Vaccine Delivery Systems Combining Biodegradability and Targeting Properties

Abstract

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(D,L-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(E-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with alpha-D-mannopyrannoside derivatives. Besides specific interaction by lectin-mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200-300 nm make them attractive candidates as vaccine delivery systems.

Glycodendrimers and Their Derivatives as Potential Therapeutic Agents

“…Compounds for bivalent presentation Fuc-(1-4)-GlcNAc (11) and N-fucosamide (12) have been also designed. [16] The search of structure-activity relationships showed, that multivalency was important for activity, in particular divalent and linear peptide analogs of the dendrimers showed strongly reduced binding at the level of monosaccharides. These investigations led to identification of dendrimer 2G3 (10) with 8 terminal fucose residues as potential glycopeptide dendrimer ligand to LecB.…”

Polyesters

“…Endocytic, cellular uptake of fl uorescently labeled particles was observed, with kinetics revealing that polyesters are endocytozed much faster than polystyrene particles [86] . Polylactide nanoparticles presenting mannose residues at their surface were prepared with dimensions of 200 -300 nm by a nanoprecipitation technique [87] . Biochemical assays were used to quantify their recognition of lectin proteins.…”

Staphylococcal enterotoxin B/texosomes as a candidate for breast cancer immunotherapy

“…Immunotherapy is a modern approach in cancer therapy leading to priming and enhancing the immune systems of cancer patients [2]. Exosomes are considered as specific cell-free vaccines in tumor immunotherapy and rejecting cancer [3]. Exosomes are membranous endosomal vesicles with the size of 30-100 nm, which are secreted from various types of normal and cancer cells [4,5].…”