117 - Cancer Targeted Nitric oxide Delivery with a Fluorescence Reporter

Abstract

Nitric oxide (NO) is a gaseous signalling molecule, which is endogenously synthesized by nitric oxide synthase (NOS) enzyme. NO mediates numerous biological processes including vasodilation, respiration, cell migration, immune response and apoptosis. Therapeutic effect of NO in cancer mainly depends on its location, concentration and rate of release. Due to the short half-life of NO, controlled generation of NO at cancer site and real time monitoring of NO is necessary.1 Although a number of methodologies for enhancement as well as detection of NO are available, these events are typically mutually exclusive. Thus, a strategy where a small molecule can generate NO in a controlled and sustained manner to the cancer cells selectively along with a fluorescence reporter would be useful for NO based cancer therapy. Elevated level of oxidative species has been found in numerous cancer cells over normal cells due to the overproduction of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), hydroxyl radical, and superoxide anion.2 Among them, H2O2 is the most stable and it has been used extensively for imaging3 as well as drug delivery4 to cancer cells. Here, we report FLUORO/NO, a new class of triggerable NO donors with an in-built fluorescence reporter. Upon activation by H2O2 in buffer, a nearly quantitative correlation between fluorescence intensity (% 2) and NO generation is observed (Figure 1). When encountered with cellular situations with varying ROS levels, FLUORO/NO is observed to preferentially generate NO in cell lines with elevated ROS levels. Therefore, FLUORO/NO is a convenient TheraNOstic tool to enhance NO selectively in cancer cells and allow real time monitoring of NO release.