Nitric oxide-releasing core-shell nanoparticles possessing silica cores and S-nitrosothiol-modified chitosan shells have been prepared. The S-nitroso groups are incorporated to the thiol-modified chitosan shell layers of the nanoparticles. The synthesis route involves two major reactions of (a) incorporation of chitosan chains to silica nanoparticles and (b) thiolation of chitosan chains. The sample made with the synthesis route which performs first the b reaction shows a higher NO-releasing amount than does the analogue prepared with the a-reaction-first synthesis route. The chemical structures and morphology of the nanoparticles have been characterized with spectral methods and electronic microscopies. The prepared sample shows a NO-releasing amount of 0.15 mu mol SNO group/mg with a prolonged NO release. (C) 2014 Elsevier Ltd. All rights reserved.