Supramolecular Assembly of a Heavy‐Atom‐Free Highly Efficient Self‐Deliverable Photosensitizer for Activable Photodynamic Therapy

Abstract

ABSTRACT This article introduces a heavy‐atom‐free, acceptor‐donor‐acceptor conjugated organic photosensitizer (ADA‐S), exhibiting an exceptional singlet oxygen ( 1 O 2 ) quantum yield (Φ∆) ∼1. The ADA‐S structure integrates two thionated naphthalene‐monoamide acceptors with a central thiophene donor moiety. To elucidate the impact of the extended conjugation on the photosensitizing efficiency, control molecules such as a less conjugated analogue (AD‐S), an acceptor‐only unit (NMIS‐Br) or an un‐thionated derivative (ADA‐O) were studied. Through the 1,3‐diphenylisobenzofuran (DPBF) assay, it was evident that ADA‐S significantly outperforms all controls in the 1 O 2 generation upon photoirradiation. Transient absorption spectroscopy studies, ranging from femtosecond‐to‐microsecond timescales revealed that extended conjugation is crucial for enhancing the triplet state longevity, which directly correlates with the observed enhancement in the 1 O 2 production. In sharp contrast, similar ADA‐type conjugated chromophore (ADA‐O), lacking thionation of the carbonyl groups, failed to produce any detectable 1 O 2 , indicating a remarkable impact of the sulphur atoms on the enhanced spin–orbit coupling, facilitating much faster intersystem crossing. Time‐dependent density functional theory calculations further supported these experimental findings, establishing ADA‐S as an outstanding new organic photosensitizer. Furthermore, an amphiphilic derivative of ADA‐S was prepared, which showed spontaneous self‐assembly in water producing nanoparticles, in which the photosensitizer remained in the dormant state due to π‐stacking. Such organic nanoparticles showed excellent cellular uptake and intra‐cellular swelling/ disassembly probed by FRET, facilitating reactivation of the photosensitization ability of the ADA‐S chromophore. Consequently, highly efficient light‐triggered cell death was noticed by reactive oxygen species.