Polymer Dots with Delayed Fluorescence and Tunable Cellular Uptake for Photodynamic Therapy and Time-Gated Imaging

By combining bioimaging and photodynamic therapy (PDT), it is possible to treat cancer through a theranostic approach with targeted action for minimum invasiveness and side effects. Thermally activated delayed fluorescence (TADF) probes have gained recent interest in theranostics due to their ability to generate singlet oxygen (¹O₂) while providing delayed emission that can be used in time-gated imaging. However, it is still challenging to design systems that simultaneously show (1) high contrast for imaging, (2) low dark toxicity but high phototoxicity and (3) tunable biological uptake. Here, we circumvent shortcomings of TADF systems by designing block copolymers and their corresponding semiconducting polymer dots (Pdots) that encapsulate a TADF dye in the core and expose an additional boron-dipyrromethene (BODIPY) oxygen sensitizer in the corona. This architecture provides orange-red luminescent particles (Φ_PL up to 18 %) that can efficiently promote PDT (¹O₂ QY=42 %) of HeLa cells with very low photosensitizer loading (IC₅₀ ~0.05-0.13 μg/mL after 30 min). Additionally, we design Pdots with tunable cellular uptake but similar PDT efficiencies using either polyethylene glycol or guanidinium-based coronas. Finally, we demonstrate that these Pdots can be used for time-gated imaging to effectively filter out background fluorescence from biological samples and improve image contrast.