Fluorescent Nanodiamonds for Light-Controlled Intracellular Heating and Nanoscale Temperature Sensing*

Subcellular thermometry is a promising tool for elucidating the role of temperature in biological processes. Especially, temperature-induced cell death has gained attention as a potential therapy for cancer where photothermal agents are utilized as subcellular heat generators to initiate cell death. To improve the efficacy of photothermal therapy (PTT), knowledge of the local temperature change that induces apoptosis is crucial. Hence, measuring such subcellular temperature change with high precision is of critical importance for diagnostics, therapeutics, and disease prognosis.

Here, we use fluorescent nanodiamonds with nitrogen-vacancy (NV) centers as a sensitive nanoscale-thermometer to report the local intracellular temperature change during photothermal therapy. We use the optically detected magnetic resonance (ODMR) of electron spins of NV defects, where the fluorescence of nanodiamonds is measured with microwave irradiation to detect the zero-field electron spin resonance of the NV ground state. The measured ODMR frequency is temperature dependent, hence by measuring the ODMR frequency shift, the temperature change can be inferred directly. Furthermore, we also measure the real-time temperature change using the NV nanothermometer, which can be used to quantitatively optimize PTT. The technique presented here shows the potential of generating and measuring local temperature change in different cellular environments using fluorescent nanodiamonds.