Diketopyrrolopyrrole–Triphenylamine\nOrganic\nNanoparticles as Multifunctional Reagents for Photoacoustic Imaging-Guided\nPhotodynamic/Photothermal Synergistic Tumor Therapy

Abstract

Herein, a donor–acceptor–donor\n(D-A-D) structured\nsmall molecule (DPP-TPA) is designed and synthesized for photoacoustic\nimaging (PAI) guided photodynamic/photothermal synergistic therapy.\nIn the diketopyrrolopyrrole (DPP) molecule, a thiophene group is contained\nto increase the intersystem crossing (ISC) ability through the heavy\natom effect. Simultaneously, triphenylamine (TPA) is introduced for\nbathochromic shift absorption as well as charge transport capacity\nenhancement. After formation of nanoparticles (NPs, ∼76 nm)\nby reprecipitation, the absorption of DPP-TPA NPs further displays\nobvious bathochromic-shift with the maximum absorption peak at 660\nnm. What’s more, the NPs architecture enhances the D-A-D structure,\nwhich greatly increases the charge transport capacity and impels the\ncharge to generate heat by light. DPP-TPA NPs present high photothermal\nconversion efficiency (η = 34.5%) and excellent singlet oxygen\n(¹O₂) generation (Φ_Δ =\n33.6%) under 660 nm laser irradiation. PAI, with high spatial resolution\nand deep biotissue penetration, indicates DPP-TPA NPs can rapidly\ntarget the tumor sites within 2 h by the enhanced permeability and\nretention (EPR) effect. Importantly, DPP-TPA NPs could effectively\nhinder the tumor growth by photodynamic/photothermal synergistic therapy <i>in vivo</i> even at a low dosage (0.2 mg/kg) upon laser irradiation\n(660 nm 1.0 W/cm²). This study illuminates the photothermal\nconversion mechanism of small organic NPs and demonstrates the promising\napplication of DPP-TPA NPs in PAI guided phototherapy.