Butterfly oscillation of an ICG dimer enables ultra-high photothermal conversion efficiency

The development of photothermal therapy (PTT) as a cancer therapy has been hampered by low photothermal conversion efficiency (PTCE), which reduces its efficacy for this application. Herein, we report the investigation of the photothermal properties of ICG-II, the dimer of indocyanine green (ICG), and show it to have an unexpectedly high PTCE of 95.6%. Based on density functional theory calculations, we attribute the high PTCE of ICG-II to changes in the relative energy levels of the occupied orbitals and a constrained “butterfly” oscillation around the dimer bond that facilitates nonradiative deexcitation. Through in vitro study, we demonstrate ICG-II to be highly biocompatible and stable to irradiation and temperatures needed for photothermal therapy. In vivo experiments show that direct injection of ICG-II followed by 2 min near-infrared (NIR) irradiation can completely eliminate xenograft tumors in mice. This work demonstrates that ICG-II is an attractive candidate for further preclinical development of photothermal agents and serves as a prototype for a class of rotationally constrained molecular rotors for PTT and other photochemical applications.