Lysosome-targetable polythiophene nanoparticles for two-photon excitation photodynamic therapy and deep tissue imaging
Two-photon excitation (TPE) photodynamic therapy (PDT) has attracted great interest due to its distinctive properties, e.g., good penetration ability of biological tissues and less damage to healthy tissue. However, the conventional photosensitizers (PSs) for PDT have poor subcellular location capability and low two-photon absorption (TPA) cross section at the phototherapeutic window. Herein, we reported a fascinating multi-functional TPE PS, polythiophene nanoparticles (PT NPs) for simultaneous lysosome-targetable fluorescence imaging and PDT. PT NPs show bright yellow fluorescence, good water solubility as well as excellent photo- and pH- stability. Moreover, PT NPs exhibit high singlet oxygen generation quantum yield (~ 42%) and large TPA cross section (~ 3420 GM). A fluorescence imaging penetration depth of 1800 μm could be reached in tissue phantom under TPE mode. Due to these outstanding merits and unique clathrin- and caveollae-independent intracellular uptake pathway, PT NPs have great potential application for TPE fluorescence imaging and photodynamic therapy.