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

This article introduces a heavy-atom-free, acceptor-donor-acceptor conjugated organic photosensitizer (ADA-S), exhibiting an exceptional singlet oxygen (1O2) 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 1O2 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 1O2 production. In sharp contrast, similar ADA-type conjugated chromophore (ADA-O), lacking thionation of the carbonyl groups, failed to produce any detectable 1O2, 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.