Donor-imine-acceptor-based small organic molecule for efficient photothermal therapy

Abstract

The development of small molecules with high photothermal conversion efficiency (PCE) poses a significant challenge in the context of photothermal therapy, a promising modality for cancer treatment. While certain efficient small molecules have been documented in the literature, they often incorporate bulky alkyl chains and/or aromatic rings to enhance the photothermal effect. Hence, this study presents a novel and straightforward method for synthesizing a photothermal small molecule, designated as PA2, utilizing a donor-acceptor framework. In this framework, diphenylamine is employed as the donor moiety, while 1,3-Bis(dicyanomethylidene)indan is utilized as the acceptor moiety. PA2 demonstrated high PCE in both monomer and but also in aggregate state. In which, the excitation energy is efficiently released as heat via non-radiative decay through the conical intersection (CI) as confirmed by a computationally optimized minimum energy crossing point (MECP) and a combination of further theoretical studies and experimental control groups (PA3 and PA4). Notably, the resulting molecular architecture exhibits remarkable efficacy in inhibiting tumor growth after a 10-day photothermal therapy period. Furthermore, in vivo experiments in a mouse tumor model demonstrate the favorable biocompatibility of these photothermal small molecules, signifying their suitability for safe application in biomedical contexts. This study makes a substantial contribution to the field of photothermal therapy by introducing a novel molecular design paradigm based on small molecules.