Photothermal Excitation of Neurons Using MXene: Cellular Stress and Phototoxicity Evaluation.

Understanding the communication of individual neurons necessitates precise control of neural activity. Photothermal modulation is a remote and non-genetic technique to control neural activity with high spatiotemporal resolution. The local heat release by photothermally active nanomaterial will change the membrane properties of the interfaced neurons during light illumination. Recently, we demonstrated that the two-dimensional Ti 3 C 2 T x MXene is an outstanding candidate to photothermally excite neurons with low incident energy per pulse. However, the safety of using Ti 3 C 2 T x for neural modulation is unknown. Here, we investigated the biosafety of Ti 3 C 2 T x -based photothermal modulation across multiple assays, including assessments of plasma membrane integrity, mitochondria stress, and oxidative stress. We demonstrated that culturing neurons on 25 μg/cm 2 Ti 3 C 2 T x films and illuminating it with laser pulses (635 nm) with different incident energies (2 - 10 μJ per pulse) and different pulse frequencies (1 pulse, 1 Hz, and 10 Hz) neither damage the cell membrane, induce cellular stress, or generate oxidative stress. The threshold energy to cause damage (i.e., 14 μJ per pulse) exceeded the incident energy for neural excitation (< 10 μJ per pulse). This multi-assay safety evaluation provides crucial insights for guiding the establishment of light conditions and protocols in clinical translation of photothermal modulation. This article is protected by copyright. All rights reserved.