Donor Modulation Brings All-In-One Phototheranostics for NIR-II Imaging-Guided Type-I Photodynamic/Photothermal Synergistic Cancer Therapy

Abstract

The type-I photodynamic (PDT) and photothermal (PTT) synergistic therapy guided by the fluorescence imaging of near-infrared region II (NIR-II) is crucial for cancer diagnosis and treatment. Phototheranostics provide a promising system for efficient imaging-guided phototherapy, which combine diagnostics with therapeutics within a single photosensitizer, avoiding complexity of composition and low reproducibility of combination methods. Herein, we design and synthesize an all-in-one phototheranostics OTAB by modifying aza-BODIPY with a methoxy group substituted triphenylamine moiety, followed by forming nanoparticle OTAB@cRGD NPs via self-assembly with DSPE-PEG2000-cRGD. Structurally, the methoxy-modified triphenylamine moiety as strong electron donor can reduce singlet−triplet energy gap (ΔES1−T1) by creating a strong intramolecular charge transfer state, thereby accelerating intersystem crossing process and thus preferentially generating O2∙- via electron transfer. A single 808 nm laser can trigger its NIR-II imaging, excellent type-I photodynamic and photothermal therapy. Furthermore, OTAB@cRGD NPs with high photostability, colloid stability and biocompatibility can actively target tumor tissue via intravenously injection. Thus, tumor localization and imaging diagnosis are successfully realized. The PDT/PTT synergistic therapy brings the efficient tumor inhibition and ablation in vitro and in vivo. Therefore, this work provides a new strategy to construct all-in-one multifunctional probe for the integration of NIR-II diagnosis and treatment.