A Unique Paradigm for a Turn-ON Near-Infrared Cyanine-Based Probe: Noninvasive Intravital Optical Imaging of Hydrogen Peroxide

Abstract

The development of highly sensitive fluorescent probes in combination with innovative optical techniques is a promising strategy for intravital noninvasive quantitative imaging. Cyanine fluorochromes belong to a superfamily of dyes that have attracted substantial attention in probe design for molecular imaging. We have developed a novel paradigm to introduce a Turn-ON mechanism in cyanine molecules, based on a distinctive change in their π-electrons system. Our new cyanine fluorochrome is synthesized through a simple two-step procedure and has an unprecedented high fluorescence quantum yield of 16% and large extinction coefficient of 52,000 M(-1)cm(-1). The synthetic strategy allows one to prepare probes for various analytes by introducing a specific triggering group on the probe molecule. The probe was equipped with a corresponding trigger and demonstrated efficient imaging of endogenous hydrogen peroxide, produced in an acute lipopolysaccharide-induced inflammation model in mice. This approach provides, for the first time, an available methodology to prepare modular molecular Turn-ON probes that can release an active cyanine fluorophore upon reaction with specific analyte.

Highly selective and sensitive surface enhanced Raman scattering nanosensors for detection of hydrogen peroxide in living cells

“…Nevertheless, these methods often cause destruction of tissues or cells, which is generally conflicting with the in-situ monitoring of H 2 O 2 in live biological samples (Lin et al, 2013;Xuan et al, 2012). By contrast, molecular fluorescence imaging through staining with a H 2 O 2 -responsive fluorescent indicator offers an attractive approach for the in vivo detection of H 2 O 2 owing to its high sensitivity and aptness for living cells (Lippert et al, 2011;Van de Bittner et al, 2010;Lee et al, 2007;Karton-Lifshin et al, 2011). However, the live-cell fluorescence imaging is usually limited severely by the photobleaching and phototoxicity induced by the excitation light (Magidson and Khodjakov, 2013).…”

Fluorescent Dyes Used in Polymer Carriers as Imaging Agents in Anticancer Therapy

“…In this manner, intramolecular charge transfer (electron rearrangement) can lead to formation of π-conjugated quinone-methide-type dye compounds (fluorochrome) with long-wavelength emission of fluorescence. These dyes (e.g., QCy7 derivatives) [168,169] can also be applied as latent fluorophore linkers of theranostic prodrugs that provide a turn-on NIR fluorescence response upon activation (Figures 20 and 21). …”

Polymeric nanotheranostics for real-time non-invasive optical imaging of breast cancer progression and drug release

“…The fluorescent signal is silenced/ ''OFF'' under physiological conditions, and is Turned-ON at a designated site and/or under specific conditions [5,17]. Although numerous classes of Turn-ON optical probes have been described in the literature for detection of chemical and biological factors [18][19][20], to this point, most polymer-based theranostic nanomedicines studies utilize an 'always ON' theranostic systems. In these systems, fluorescent signal is obtained from the background and desired signal at once, resulting in low TBR.…”

“…Under these circumstances the emitted energy from one fluorophore is absorbed by another fluorophore [23]. A third approach is to employ changes in the push-pull conjugated p-electron system of the dye [18,24]. The energy that was absorbed or emitted during a fluorescence process occurs as a result of the specific small gaps of conjugated p electrons energy levels.…”