Nitric Oxide Releasing Photoresponsive Nanohybrids As Excellent Therapeutic Agent for Cervical Cancer Cell Lines Priya Sudhesh, Kaviyarasan Tamilarasan, Palaniappan Arumugam, and Sheela Berchmans* Electrodics and Electrocatalysis Division, CSIR-Central Electrochemical Research Institute, Karaikudi, Tamilnadu 630006, India * S Supporting Information ABSTRACT: Gold nanoparticles (GNPs) that can release nitric oxide (NO) on visible-light irradiation were prepared using 2-mercapto-5-nitro benzimidazole (MNBI) as stabilizer. These nanoparticles meet overall prerequisites for biomedical applications like small sizes, water solubility, and stability. It was found that even a very low dosage of MNBI-stabilized GNPs exhibit appreciable tumor cell mortality against cervical cancer cell lines, demonstrating the role of NO in killing cancer cells. KEYWORDS: photoresponsive, nanohybrids, 2-mercapto-5-nitrobenzimidazole (MNBI), gold nanoparticles (GNP), nitric oxide (NO), apoptosis ■ INTRODUCTION Nitric oxide (NO) is a fascinating molecule, because of its key role in several physiological processes. 1 The exciting discoveries of multiple roles of NO in physiological processes such as neurotransmission, vasodilation and hormone secretion, has led to a prolific growth in the area of synthesis of NO delivering materials. 2-5 Also NO proved to be an excellent antioxidant in free radical induced lipid peroxidation and an efficient anticancer agent. 6-8 High level expression of NO produced by activated macrophages may be cytostatic or cytotoxic for tumor cells but low level expression can have opposite effect and can promote tumor proliferation. 7 So the investigation of the role of NO in cancer at the molecular level can have profound effect on its treatment and therapeutic application. Many classes of NO donors are known viz., nitrosothiols (RSNOs), 9 diazeniumdiolates (NONOates), 10-12 4-alkyl-2- hydroxyimino-5-nitro-3-hexenes (NORs), 13-15 etc. These compounds release NO by autolysis. Substances that release NO by light stimuli were found to be more attractive than those based on autolysis. The easy manipulation of light along with the fast response of NO release by photochemical reactions allows one to have temporal and targeted NO delivery. Benzimidazole nucleus acts as the key building block for developing molecules of pharmaceutical and biological interest. 16-19 Nitro benzimidazole derivatives have been reported as efficient antitumor compounds by Ramla et.al and the studies show that the cytotoxic effect is mainly due to the presence of nitro goup. 18 Herein, we report on the synthesis of 2-mercapto-5-nitro benzimidazole (MNBI)-capped GNPs in aqueous conditions which are intended to release NO under visible-light irradiation in controlled fashion. In the present case, benzimidazole acts as bridging ligand between chromo- phore (NO 2 ) and gold core. The synergistic effect of high surface to volume ratio of GNPs along with its water solubility and light-induced NO release are taken as advantages in designing a potent therapeutic agent against cervical cancer cell lines. ■ RESULTS AND DISCUSSION The aqueous soluble 2-mercapto-5-nitro benzimidazole stabi- lized gold nanoparticles (MNBI-GNPs), prepared in our lab, showed enhanced antitumor efficacy against cervical cancer cell lines (HeLa) (Scheme 1). The synthesis of water-soluble MNBI stabilized GNPs was achieved by borohydride reduction method. This method involves a simple two step procedure (Supporting Information) in which tetrachloroauric acid was mixed with MNBI in alkaline Received: May 31, 2013 Accepted: August 16, 2013 Scheme 1. Schematic Representation Showing HeLa Cell Apoptosis in the Presence of MNBI-Stabilized GNPs Letter www.acsami.org © XXXX American Chemical Society A dx.doi.org/10.1021/am402086m | ACS Appl. Mater. Interfaces XXXX, XXX, XXX-XXX