Stimuli-Responsive Reversible Switching of Intersystem Crossing in Pure Organic Material for Smart Photodynamic Therapy

Photosensitizers (PSs) with stimuli-responsive reversible switching of intersystem crossing (ISC) are highly promising for smart photodynamic therapy (PDT), but achieving this goal remains a tremendous challenge. This study introduces a strategy to obtain such reversible switching of ISC in a new class of PSs, which exhibit stimuli-initiated twisting of conjugated backbone. We present a multidisciplinary approach that includes femtosecond transient absorption spectroscopy and quantum chemical calculations. The organic structures reported show remarkably enhanced ISC efficiency (phi(ISC)), switching from nearly 0 to 90 %, through an increase in the degree of twisting, providing an innovative mechanism to promote ISC. This leads us to propose here and demonstrate the concept of smart PDT, where pH-induced reversible twisting maximizes the ISC rate, and thus enables strong photodynamic action only under pathological stimulus (such as change in pH, hypoxia, or exposure to enzymes). The ISC process is turned off to deactivate PDT ability, when the PS is transferred or metabolized away from pathological region.