In Vivo Electrochemical Detection of Nitroglycerin‐Derived Nitric Oxide in Tumor‐Bearing Mice

Abstract

The ability of an inserted electrode to detect in vivo NO in tumor was achieved by using a chemically modified Pt/Ir electrode as NO-sensor and nitroglycerin NTG as NO donor. Enzymatically induced release of NO from NTG was tracked in the tumor, upon intra peritoneal injection of NTG. This approach allowed in vivo monitoring of the bioavailability of NO and could be applied to the in vivo study of candidate anticancer drugs acting on the NO pathways.Keywords: Tumor, In vivo detection, Nitric oxide, Nitroglycerin, NO-sensor, Electrochemical detection DOI: 10.1002/elan.200804300 Tumor vasculature plays an essential role in tumor survival and development, leading to the concepts of antiangiogenic and antivascular therapy [1 -3]. While the antiangiogenic strategy targets the formation of tumor new vessels, the antivascular drugs aim at targeting the existing tumoral vasculature and at causing tumor endothelial cells death [4]. One of the principal actors in the antivascular approach appears to involve the action of nitric oxide (NO) [2 -6]. Thus, it is believed that this induced NO-release could be considered, at least partially, as an in vivo marker of the anticancer activity of this class of agents. Interest in elucidating the mechanism of action of several classes of anticancer agents and also in exploring the pathways of the induced-NO release provides an impetus for conceiving a well-designed approach to locally detect NO in tumors, in vivo. Measuring NO from liquid samples is now well documented [7] and the electrochemical detection systems are recognized as being the only reliable analytical method to determine NO local concentration in real time, without disturbing its metabolism and its associated regulatory pathways [8,9].We recently extended the use of the electroanalytical concept and adapt it to a very special and complex biological tissue such as tumors [10]. We have demonstrated that miniaturized electrochemical sensor can be used in vivo for probing electroactive species in tumor-bearing mice. This was first achieved by performing for the first time in vivo cyclic voltammetry of K 4 Fe(CN) 6 . In addition, the use of two NO donors allowed, for the first time, to demonstrate the feasibility of the electrochemical detection of directly injected exogenous NO in live tumor-bearing mice.Nitroglycerin (NTG) is one of the oldest NO donors reported in the literature. It is enzymatically metabolized in living systems and the produced NTG-derived NO diffuses into the surrounding tissues [11,12]. Thus, the change in basal level of NO through induced enzymatically decomposed NTG constitutes a pertinent approach to explore our electroanalytical methodology to footpath intra tumoral NO. This led us to explore the monitoring of changes in the intra tumoral NO levels upon intra-peritoneal injection of NTG. Thus, in this work we report for the first time on the local in vivo tracking of changes in level of NTG-derived NO in tumor bearing mice in order to path the way for future studies of the evaluation of ...

Electrochemical Sensors for Nitric Oxide Detection in Biological Applications

“…This inserted sensor successfully measured NO concentration changing in tumor bearing mice by directly injected NONOate into the tumor tissue 44. In addition, their group used the same sensor in vivo for electrochemical detection of NO in tumor‐bearing mice by intra peritoneal injection of nitroglycerin 138. These sensors could be applied to the in vivo study of candidate anticancer drugs acting on the NO pathways.…”

Highly Sensitive Nitric Oxide Sensing Using Three‐Dimensional Graphene/Ionic Liquid Nanocomposite

“…Nitric oxide (NO) is a biological signalling molecule and plays an important role in the regulation of cell function of the nervous, vascular and immune systems [1][2][3], such as functioning as a neurotransmitter [4], modulating vasodilation [5] and the action of macrophages [6]. It is also implicated in the parthenogenesis of these systems as seen in tumour angiogenesis [7] and Parkinsons disease [8].…”

Au Nanoparticles–3D Graphene Hydrogel Nanocomposite To Boost Synergistically in Situ Detection Sensitivity toward Cell-Released Nitric Oxide

“…However, chemiluminescence requires additional reagents to react with NO as a luminous source and a fluorescent or a spin-trapping NO compound for generating detectable signals and has poor selectivity . Fluorometric assays are not reproducible, and some probes are pH-sensitive, affecting the sensitivity of the method. , ESR needs special handling and specific experimental conditions, such as low temperature operation and long recording time. , In contrast, the electrochemical method is simple, sensitive, portable, selective, fast, and miniaturizable; , thus, it is an advantageous method to achieve real-time and in situ monitoring of nitric oxide in biological samples. ,, …”