Quantitative Evaluation of Light-to-Heat Conversion and Singlet Oxygen Generation Efficiencies on Ligand Protected Gold Nanoclusters upon Near-infrared Excitation

Abstract

Two-photon absorbing materials exhibiting both photothermal and photodynamic effects under near-infrared (NIR) light irradiation are of great interest for deep-tissue phototherapy. However, a persistent challenge in the field is the lack of standardized metrics for quantitatively comparing photothermal agents and photodynamic agents across different excitation regimes (from continuous wave to pulsed regimes of operation in femtosecond laser). Herein, we address this challenge by developing unified models under both one- and two-photon excitation to quantitatively assess light-to-heat conversion and singlet oxygen generation efficiencies and for this purpose, we report the synthesis and comprehensive physicochemical characterization of atomically precise Au NCs, Au25(pMBA)18, Au102(pMBA)44, as well as larger Au NCs featuring nascent surface plasmon-like resonance, Au∼288(pMBA)∼92 (pMBA = 4-mercaptobenzoic acid). The two-photon absorption cross section of these Au NCs in water was deduced from the P-scan measurements to range from 9×105GM to 700×105 GM under 808 nm femtosecond laser excitation. Comparative investigations quantitatively reveal pronounced size-dependent differences in photothermal and photodynamic trends under NIR excitation. Photothermal efficiency follows the order: Au~288 > Au102 ≫ Au25, whereas the singlet oxygen (1O2) generation efficiency exhibits the opposite trend: Au25> Au102 ≫ Au~288. These contrasting behaviors highlight distinct underlying mechanisms governing photothermal and photodynamic processes: the discrete electronic structures and excited-state dynamics of small Au NCs (Au25 and Au102) predominantly dictate photodynamic activity, while nascent surface plasmon resonance of larger Au NCs (Au~288) enhance hyperthermic responses. Moreover, these NCs exhibit excellent biocompatibility toward HeLa cancer cells, underlining their potential as dual-mode two-photon phototherapeutic agents for deep-tissue biomedical applications.