Micro- and nanoparticle-supported lipid assemblies have significant potential for being used in biology and medicine for sensing, mimicking cellular membranes, and delivering drugs or cosmetic agents. Here, we introduce a new type of nanohydrogels based on the modification of a polysaccharide with lipid moieties, followed by the formation of nanoparticles and assembling lipid bilayers on the particle surfaces. The lipophilic compound 1,2-ditetradecanoyl-sn-glycero-3-phosphoethanolamine (DMPE) and the UV-crosslinkable methacrylic anhydride were covalently attached to hyaluronic acid (HA) and the formation of hydrogel nanoparticles via a surfactant-free inverse emulsion mechanism was demonstrated. As an anchoring group, the lipophilic DMPE moiety enables the formation of hydrogel nanoparticles with a spherical morphology in nonpolar media and allows for the stable assembly of lipid bilayers bearing amphiphiles on HA nanohydrogel surfaces. The conjugated oligoelectrolyte, 4,4'-bis[4'-(N,N-bis(6 ''-(N,N,N-trimethylammonium)hexyl)amino)styryl] stilbene tetraiodide (DSSN+), was incorporated into the nanohydrogel-supported lipid bilayers, resulting in the formation of stable multilamellar peripheral vesicular structures due to the similarity in chemical structure of DMPE and the assembled lipid molecules. (C) 2014 Elsevier B.V. All rights reserved.