Abstract
Temperature is an essential parameter in all biological systems, but information about the actual temperature in living cells is limited. Especially, in photothermal therapy, local intracellular temperature changes induce cell death but the local temperature gradients are not known. Highly sensitive nanothermometers would be required to measure and report local temperature changes independent of the intracellular environment, including pH or ions. Fluorescent nanodiamonds (ND) enable temperature sensing at the nanoscale independent of external conditions. Herein, we prepare ND nanothermometers coated with a nanogel shell and the photothermal agent indocyanine green serves as a heat generator and sensor. Upon irradiation, programmed cell death was induced in cancer cells with high spatial control. In parallel, the increase in local temperature was recorded by the ND nanothermometers. This approach represents a great step forward to record local temperature changes in different cellular environments inside cells and correlate these with thermal biology.
Highlights
Temperature plays a fundamental role in biological processes of living organisms and is involved in cell differentiation, proliferation, and death,[1] protein functions,[2,3] and gene expression.[4]
We have recently reported the stabilization of NDs in a cross-linked nanogel (ND-NG) that were nontoxic in cell experiments.[33]
We found that the temperature increased sharply by more than 30 °C and was saturated after approximately 250 s of irradiation for the ND-NG-indocyanine green (ICG) samples, whereas there was no significant change in temperature in the ND-NG samples under irradiation
Summary
Temperature plays a fundamental role in biological processes of living organisms and is involved in cell differentiation, proliferation, and death,[1] protein functions,[2,3] and gene expression.[4]. The intracellular localization of ND-NG-ICG was imaged after incubating HeLa cells for 4 h with two different nanoparticle concentrations, 10 and 100 μg/mL (Figure S10). To measure the intracellular changes in the local temperature at the nanoscale under irradiation, HeLa cells were cultured on an autoclaved glass coverslip, which was placed in a 12-well cell culture plate and incubated overnight. We propose that cells could compensate for a pronounced local temperature increase if only a few heating sources of a low concentration of ND-NG-ICG are present In this way, our results are in line with other reports: i.e., on mitochondria, which can tolerate comparatively high temperatures without affecting cell viability.[10] In contrast, the presence of many local ND-NGICG heating sources (100 μg/mL), which produced heat over a larger volume in the cell, effectively induced cell death. Quantifying the number of NDs from the fluorescence signal is not possible
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