Photothermal-Actuated Thermoelectric Therapy by Harnessing Janus-Structured Ag–Ag2S Nanoparticles with Enhanced Antitumor Efficacy

The newly developed thermoelectric dynamic therapy (TEDT) may not only solve the problem that photothermal therapy (PTT) is limited by the overexpression of heat shock proteins (HSPs) in tumor cells but also improve the killing effect through a dynamic process. Here, we propose photothermal-driven TEDT based on Ag–Ag2S nanoparticles that integrate Ag2S with Ag+ vacancies (VAg) and Ag in a Janus structure. VAg and Ag optimize the band structure and thermoelectric properties of Ag2S, and additional electrons from the introduction of Ag enhance the PTT effect and facilitates the construction of a significant thermoelectric field for electron–hole migration in the reverse direction, thereby markedly enhancing the TEDT effect. Furthermore, the generated VAg can also serve as a hole trap to suppress electron–hole recombination to promote 1O2 production, which inactivates HSPs to produce positive feedback on PTT, leading to better antitumor efficacy. The combined photothermal–thermoelectric therapeutic properties of Ag–Ag2S were verified from both in vivo and in vitro perspectives using ESR, UV–visible spectroscopy, cellular experiments, simulated tumor models, and other experiments.