Molecular thermometers for potential applications in thermal ablation procedures

Abstract

Thermal ablation is a promising minimally invasive method for treating tumors without surgical intervention. Thermal ablation uses thermal sources such as lasers, radiowaves or focused ultrasound to increase the temperature of the tumor to levels lethal to cancer cells. This treatment based on heat therapy may be problematic as the temperature of the operation site is unknown. To address this problem, we developed optical molecular thermometers that can potentially measure the temperature on a molecular scale and be compatible with in vivo measurements. The thermometers are centered on a combination of two fluorophores emitting in two distinct spectral ranges and having different temperaturedependent emission properties. In this design, a fluorophore with relatively insensitive temperature-dependent fluorescence serves as a reference while another sensitive fluorophore serves as a sensor. We have demonstrated the feasibility of this approach using a coumarin-rhodamine conjugate. The sensitivity of the construct to the clinically relevant ablation temperatures (20-85 ºC) was demonstrated in vitro.

Nanothermometry: From Microscopy to Thermal Treatments

“…[30] Coumarin, with as trong temperature sensitivity (6.6 %K À1 ), and rhodamine 640, with almost no thermalr esponse (< 0.1 %K À1 ), were covalently connected to each other.T om inimize the fluorescence energy transfer that complicates the readout,t hesed yes were selected from different spectral ranges,s ince this preventeds pectralo verlap. [30] Coumarin, with as trong temperature sensitivity (6.6 %K À1 ), and rhodamine 640, with almost no thermalr esponse (< 0.1 %K À1 ), were covalently connected to each other.T om inimize the fluorescence energy transfer that complicates the readout,t hesed yes were selected from different spectral ranges,s ince this preventeds pectralo verlap.…”

“…To alleviatet his problem,o ur lab has explored as trategy of assembling two fluorophores with different thermals ensitivities into as ingle construct. [30] Coumarin, with as trong temperature sensitivity (6.6 %K À1 ), and rhodamine 640, with almost no thermalr esponse (< 0.1 %K À1 ), were covalently connected to each other.T om inimize the fluorescence energy transfer that complicates the readout,t hesed yes were selected from different spectral ranges,s ince this preventeds pectralo verlap. The ratio of the two emissions provided the basis for temperature measurement.…”

“…Dependence of the autocorrelation curve of rhodamine 6G in ethylene glycol on the temperature induced by NIR laser light. [43] ChemPhysChem 2016, 17,[27][28][29][30][31][32][33][34][35][36] www.chemphyschem.org et al [54] prepared as ensor based on ac onjugated porphyrin dimer that is capable of decoupling temperature from viscosity effects and therefore, enables accurate temperature measurements in viscousenvironments.…”

Fluorescence anisotropy (polarization): from drug screening to precision medicine

“…3). An opposite effect of temperature on dyes is decreasing the fluorescence lifetime, especially in molecules with strong thermal sensitivity such as certain coumarines 50 or cyanine dyes. 51 Overall, the role of temperature is difficult predict, 52 but needs to be controlled in order to generate reproducible results.…”

Design of Fluorescent Nanocapsules as Ratiometric Nanothermometers

“…[14a, 15] Thus, we recently investigated a two-fluorophore system where two fluorophores emitting at two different wavelengths were covalently conjugated to each other. [16] In that approach, a fluorescent visible dye, coumarin, with a strong temperature sensitivity (6.6 %·K −1 ) was conjugated to a dye rhodamine 640 (Rho640) with almost no thermal sensitivity (<0.1%·K −1 ). The overall response of the construct, however, showed only a marginal thermal sensitivity of 0.5%·K −1 , near the limit of a recently introduced “quality threshold” for thermometers.…”