Rational design of an “all-in-one” phototheranostic

Phototheranostics integrate both optical-based imaging modalities and light-based therapies into one single molecular entity. In principle, this strategy could enhance the precision of disease diagnosis and treatment through the simultaneous imaging of diseased tissue, monitoring of drug delivery, and evaluation of therapeutic efficacy. This may allow treatments to be tailored to an individual patient (personalized medicine). Here, we report porphodilactol derivatives and their corresponding metal complexes that show promise as “all-in-one” phototheranostics. They are predicated on a design strategy that involves controlling the relationship between intersystem crossing (ISC) and photothermal conversion efficiency following photoexcitation. The requisite balance was achieved by tuning the aromaticity of these porphyrinoid derivatives and forming complexes with one of two lanthanide cations, namely Gd3+ and Lu3+. The net result led to a metalloporphodilactol system, Gd-trans-2, with seemingly optimal ISC efficiency, photothermal conversion efficiency and fluorescence properties, as well as good chemical stability. In the context of this study, we discovered that the exocyclic β-hydroxyl unit present in Gd-trans-2 was essential for the Type I production of reactive oxygen species (ROS) under near-infrared (NIR) photo-irradiation. This subunit is believed to mediate proton coupled electron transfer (PCET) between the porphyrinoid excited state and molecular oxygen. Finally, encapsulation of Gd-trans-2 within mesoporous silica nanoparticles (MSN) allowed its evaluation for tumor diagnosis and therapy. It was found to be effective as an “all-in-one” phototheranostic that allowed for NIR fluorescence/photoacoustic dual-modal imaging while providing an excellent combined PTT/PDT therapeutic efficacy in vitro and in vivo in 4T1-tumor-bearing mice.