Donor modulation brings all-in-one phototheranostics for NIR-II imaging-guided type-I photodynamic/photothermal synergistic cancer therapy

Type-I photodynamic (PDT) and photothermal (PTT) synergistic therapy guided by fluorescence imaging in the near-infrared region II (NIR-II) is crucial for cancer diagnosis and treatment. Phototheranostics provide a promising system for efficient imaging-guided phototherapy, combining diagnostics with therapeutics within a single photosensitizer and avoiding the complexity of composition and low reproducibility of combination methods. Herein, we design and synthesize an all-in-one phototheranostic agent OTAB by modifying aza-BODIPY with a methoxy group substituted triphenylamine moiety, followed by the formation of nanoparticle OTAB@cRGD NPs via self-assembly with DSPE-PEG2000-cRGD. Structurally, the methoxy-modified triphenylamine moiety as a strong electron donor can reduce the singlet-triplet energy gap (Delta ES1-T1) by creating a strong intramolecular charge transfer state, thereby accelerating the intersystem crossing process and thus preferentially generating O2(center dot)-via electron transfer. A single 808 nm laser can trigger its NIR-II imaging and excellent type-I photodynamic and photothermal therapy. Furthermore, OTAB@cRGD NPs with high photostability, colloid stability and biocompatibility can actively target tumor tissue via intravenous injection. Thus, tumor localization and imaging diagnosis are successfully realized. The PDT/PTT synergistic therapy brings efficient tumor inhibition and ablation both in vitro and in vivo. Therefore, this work provides a new strategy to construct an all-in-one multifunctional probe for the integration of NIR-II diagnosis and treatment.