Heavy Atom-Free, Mitochondria-Targeted, and Activatable Photosensitizers for Photodynamic Therapy with Real-Time In-Situ Therapeutic Monitoring

Based on spin-orbit charge transfer intersystem crossing mechanism, two heavy-atom-free photosensitizers (PSs) BDP1/BDP2 with absorption maxima at 506 nm/660 nm were constructed for photodynamic therapy (PDT). The long triplet state lifetimes and large singlet oxygen quantum yields, coupled with the mitochondria-targeted feature, made them highly phototoxic toward cancer cells. Moreover, the PDT-promoted cell apoptosis could be monitored by an obvious fluorescence off-on response of the two PSs due to the concomitant activation of extensive mitophagy, thus facilitating timely therapeutic feedback to avoid under- or over-treatment. Importantly, such design allows the activatable PSs Glu-BDP1/Glu-BDP2 to be fabricated by attaching gamma-glutamyl, a substrate of gamma-glutamyltranspeptidase, to the alkoxyaniline unit of BDP1/BDP2, and their ability in either selectively killing cancer cells over normal cells or in ablating implanted tumour without damage to healthy tissue was demonstrated.