Nitric oxide imaging in cancer enabled by steric relaxation of a photoacoustic probe platform

Abstract

Nitric oxide (NO) is a key signaling molecule involved in a variety of physiological and pathological processes. Over the past few decades it has become clear that the microenvironment and concentration of NO are critically linked to its bioactivity. Direct visualization of NO in vivo remains difficult due to a lack of sensitive analytical tools with deep tissue compatibility. Herein, we report the optimization of an activatable photoacoustic probe for NO by planarizing the boron-azadipyrromethene (aza-BODIPY) dye platform via steric relaxation. The lead compound, SR-APNO-3, exhibits maximal absorption at 790 and 704 nm before and after N-nitrosation with NO, respectively, and a 4.4-fold increase in the theoretical maximal ratiometric response compared to the non-sterically relaxed parent compound, APNO-5. This circa 30 nm red-shift enabled direct visualization with the laser system commonly employed in commercially available photoacoustic tomographers and a 1.1-fold increase in sensitivity within an intramuscular lipopolysaccharide-induced inflammation model. Moreover, this optimization facilitated the detection of endogenously produced NO in an allograft murine breast cancer model, where steadystate concentrations are several orders of magnitude less than during the immune response.

Highly Stable Organic Photothermal Agent Based on Near-Infrared-II Fluorophores for Tumor Treatment

“…S4). The size of NIR998 NPs in PBS contributed to their accumulation at tumor parts by the EPR effects [20]. In addition, NIR998 NPs solutions exhibited similar hydrodynamic diameter for half a month in refrigerator at 4 °C ( Fig.…”

New directions of activity-based sensing forin vivoNIR imaging

“…88 Important criteria to consider in the design of an ABS probe for PA imaging are the following: a l abs in the NIR window, high extinction coefficient, low uorescent quantum yield, and for ratiometric probes, minimal overlap between the absorbance proles. [89][90][91] Using these criteria, a variety of ABS probes have been developed for Cu 2+ , 92 hypoxia, 93,94 nitric oxide, 95,96 and a variety of enzyme targets. [97][98][99][100] This is in addition to many excellent non-ABS PA probes that have been reviewed elsewhere.…”

Highly stable organic photothermal agent based on near-infrared-II fluorophores for tumor treatment

“…Aza-BODIPY as an inherent photothermal agent was chosen as thevresearch object [22], and aza-BODIPYs with D−A−D structures, especially, with alkyl aniline parts serving as a strong electron donor, exhibit satisfactory NIR-I absorption and emission [23]. In addition, an electron donor with small steric hindrance can also boost the redshifted absorption and emission capability of aza-BODIPYs core via the steric relaxation effect [24]. Thus, diethylamine, which has a strong donor electronic ability, is introduced at positions 3 and 5 of aza-BODIPYs core, where it achieves the optimal effect of reducing the energy gap for red-shifted absorption and emission [25].…”