Fluorescent chitosan complex nanosphere diazeniumdiolates as donors and sensitive real-time probes of nitric oxide

Abstract

A new CuFL (2-{2-chloro-6-hydroxy-5-[(2-methyl-quinolin-8-ylamino)-methyl]-3-oxo-3H-xanthen-9-yl}-benzoic acid)–CS (chitosan) NS diazeniumdiolates system consisting of NO donors and highly-sensitive NO probes is reported. FL–CS NS diazeniumdiolates were synthesized by incorporating the fluorescent molecule FL with chitosan (CS) and reacting the resultant FL–CS complex with pressurized NO and dimethyl sulfate (DMS). Then the FL–CS NS diazeniumdiolates were reacted with copper chloride (CuCl₂) to generate non-fluorescent CuFL–CS NS diazeniumdiolates. The CuFL–CS NS diazeniumdiolates have a spherical outline with a dimension of ca. 250 nm. They have high selectivity for NO over other related substances. The results of in vitro and in vivo experiments indicate that the CuFL–CS NS diazeniumdiolates can release NO under physiological conditions and meanwhile detect the released NO based on the considerable fluorescence increase of the otherwise non-fluorescent system caused by the NO. The good fluorescence stability of the NO–FL–CS NS provides prospects for the CuFL–CS NS diazeniumdiolates in biomedical applications.