Bridging Atom Engineering of Naphthalene Diimide-Based Semiconducting Polymer Dots for NIR-II Imaging-Guided Tumor Photodynamic and Photothermal Therapy

Near-infrared second-window fluorescence imaging (NIR-II FI)-guided synergistic photothermal therapy (PTT) and type-I photodynamic therapy (PDT) hold great promise for noninvasive tumor treatment. However, it is remains highly challenging to develop phototheranostic agents with desired performances, and the systematic exploration of naphthalene diimide (NDI)-based conjugated polymers in this field is still limited. Herein, three NDI-based semiconducting polymers (Si-NDI, C-NDI, and N-NDI)-derived Pdots with various bridge atoms (C, N, and Si) in the cyclopentadithiophene donor units are rationally constructed by nanoprecipitation. These Pdots exhibit uniform spherical morphologies with hydrodynamic diameters of ∼30−40 nm, excellent colloidal stability, and efficient passive tumor targeting via the enhanced permeability and retention (EPR) effect. Among them, C-NDI Pdots exhibit the most superior performance, including robust NIR-II fluorescence, efficient type I reactive oxygen species (O2•−/•OH) generation, and high photothermal conversion efficiency (58.8%). The as-prepared C-NDI Pdots are further applied for efficient tumor cell ablation in vitro and achieve NIR-II imaging-guided synergistic PTT/PDT tumor ablation in 4T1 tumor-bearing nude mouse with satisfactory results. We believe that this work not only provides outstanding NDI Pdots-based phototheranostic nanoagents for non-invasive tumor treatment but also offers a bridge atom tuning strategy for the design of high-performance multimodality phototheranostic nanoagents.