Article pubs.acs.org/Langmuir
Controllable Nitric Oxide Release in the Presence of Gold Nanoparticles Patricia Taladriz-Blanco,† Vicente Pastoriza-Santos,‡ Jorge Pérez-Juste,*,† and Pablo Hervés*,† †
Departamento de Química Física and ‡Departamento de Tecnología Electrónica, Universidade de Vigo, 36310 Vigo, Spain S Supporting Information *
ABSTRACT: A major problem associated with nitric oxide (NO) donors is the release of the desired amount of NO at a specific site. A number of platforms have been developed for the regulation of NO dosage. We present the use of citrate-stabilized gold nanoparticles as a platform to regulate NO release. Because of the affinity between gold and thiols, the characteristic −S−NO bond of S-nitrosothiols (RSNOs) breaks in the presence of gold nanoparticles, thereby releasing NO and modifying the gold nanoparticle surface with the corresponding thiol. This system allows for surface-controlled NO release, where the amount of NO released is proportional to the number of thiols bound to the gold nanoparticle surface. Moreover, by employing an amperometric technique to detect the maximum NO release, we were able to estimate the stoichiometry of the reaction, that is, the number of adsorbed RSNO molecules per gold nanoparticle. A kinetic model for NO release and its subsequent decomposition is proposed and used to fit the experimental results. The reaction was found to be zeroth- and firstorder with respect to RSNO and gold nanoparticles, respectively.
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conditions.13 Recently, suitable macromolecular drug carriers such as silica nanoparticles,14 metallic nanoparticles,15 polyelectrolytes,16 and polymers17 have been loaded with NO donor moieties to enable larger reservoirs of deliverable NO.18 In addition, the light-induced generation of nitric oxide was recently discussed.19 Controllable NO photorelease in a small area has been found in the case of nanoparticles,20 selfassembled monolayers,21,22 polymer films,23 gels,24,25 and micelles.26 For instance, Ho et al. explored the ability of NO to be readily adsorbed on alkanethiolate-protected ruthenium nanoparticles. Subsequently, they demonstrated that adsorbed NO could be released in a controlled way upon visible-light irradiation.27 We recently demonstrated the surface modification of citratestabilized gold nanoparticles with DL-penicillamine (PEN) and N-acetyl-DL-penicillamine (NAP) through the thiol functionality.28 It should be pointed out that both thiol-containing amino acids can be easily nitrosated to the corresponding nitrosothiols.29 Taking into account that the dissociation energy of the gold thiol (RS−Au) bond is greater than that of the RS− NO bond (40 versus 20 kcal mol−1),30,31 it is feasible that the S−N bond can be easily cleaved in the presence of AuNPs, favoring S−Au bond formation and the subsequent release of nitric oxide.32 This work is focused on the study of the goldnanoparticle-mediated release of NO from low-molecularweight RSNOs such as S-nitrosopenicillamine (SPEN), S-
INTRODUCTION It is well-known that NO plays a fundamental role in the regulation of biological processes, including neurotransmission, hormone secretion, and vasodilation in living bodies.1−3 Furthermore, the efficiency of NO as an antimicrobial4,5 agent and tumoricidal6 factor have rendered NO a promising pharmaceutical agent. However, it should be noted that the biological effects of nitric oxide are highly dependent on concentration and dosage, creating a complex role for the molecule in opposing beneficial and deleterious effects.7,8 This complicated behavior demands new methods for generating NO in a controlled manner, to facilitate both an improved understanding of the function of NO in physiology and the development of NO-associated therapies.9 In response to the need for controlled NO delivery, much work has focused on the synthesis of NO donors. Many classes of NO donors exist, including alkyl nitrites, transition-metal nitrosyl complexes, nitrosamines, N-diazoniumdiolates, and Snitrosothiols (RSNOs).9 RSNOs represent one of the most widely used NO donor systems, because they decompose thermally and photochemically to give the corresponding disulfide and nitric oxide. An additional route is the coppercatalyzed decomposition of S-nitrosothiols at physiological pH giving rise to the same products.10 RSNOs have much the same physiological properties as NO itself, particularly vasodilation and the inhibition of platelet aggregation.11 They have also been identified in bodily fluids, notably as S-nitrosoglutathione and S-nitrosoalbumins.12 Indeed, the current belief is that NO is transported around the body as RSNOs (mostly as the Snitrosoalbumins) from which NO can be released under certain © XXXX American Chemical Society
Received: December 7, 2012 Revised: May 21, 2013
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dx.doi.org/10.1021/la4014762 | Langmuir XXXX, XXX, XXX−XXX
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MICRO GLASS COMB pH electrode or a Hanna Instruments pH 210 pH meter equipped with a VWR 662-1759 glass electrode. NO release was measured with a World Precision Instrument ISO-NO meter equipped with a data acquisition system based on direct amperometric detection of NO with a short response time (
