Hypothesis: For some years, smart nano-objects are one of the main focuses of current research. In the framework of polymeric nanomedicine, o-nitrobenzyl alcohol derivatives lead to light-responsive polymeric materials. At this day, nanomedicine based on polysaccharide/poly(o-nitrobenzyl acrylate) (PNBA) copolymers have never been reported. Experiments: For the first time, PNBA core/dextran shell nanoparticles (NPs) were formulated by evaluating two different processes: (i) nanoprecipitation of preformed Dextran-g-PNBA glycopolymers, (ii) emulsion/evaporation using azido-functionalized PNBA and alkynated dextran, carrying out (or not) an interfacial click chemistry reaction. NPs' characterization, colloidal stability in the presence of salts and of an anionic competitive surfactant (SDS) and light-induced disruption were assessed. Finally, the potential use of these NPs as photo-responsive drug delivery systems was investigated by a preliminary in vitro cytotoxicity study using Caco-2 cells. Findings: Whatever the process, the photosensitive property and the colloidal stability of NPs in the presence of salts were proved. However, triazole rings between the dextran shell and the PNBA core avoid the dextran shell desorption in the presence of SDS. NPs' biocompatibility towards Caco-2 was proved and 100% cell viability was still observed after exposure to NPs following by 60 s UV-irradiation. (C) 2017 Elsevier Inc. All rights reserved.