Diketopyrrolopyrrole-Au(I) as singlet oxygen generator for enhanced tumor photodynamic and photothermal therapy

Diketopyrrolopyrrole (DPP) derivatived photosensitizers (PSs) with near infrared (NIR) absorption and good photophysical properties have drawn tremendous attention in cancer phototherapy. However, current DPP derivatives present unsatisfactory quantum yield of singlet oxygen (¹O₂) due to the large energy gap between the excited singlet and triplet states. To tackle this challenge, herein the DPP core is functionalized with triphenylphosphine-Au(I) group (ThDPP-Au), leading to a high ¹O₂ quantum yield of 0.65. Theoretical calculation attributes the enhancement to spin-orbit coupling and population of the triplet excition upon photoexcitation. The hydrophilic ThDPP-Au nanoparticals (NPs) are prepared via nano-reprecipitation, which displays homogeneous size and excellent light absorption ability (ε=4.382×10⁴ M⁻¹ cm⁻¹). And the ThDPP-Au NPs exhibit low dark toxicity and high phototoxicity, which can effectively kill tumor cells via ¹O₂ induced mitochondrial apoptotic pathway upon irradiation. Furthermore, in vivo experiments demonstrate that ThDPP-Au NPs can selective accumulation in tumor and present excellent synergistic photodynamic/photothermal therapy guided by fluorescence and photothermal dual imaging.