Utilizing Intramolecular Photoinduced Electron Transfer to Enhance Photothermal Tumor Treatment of Aza-BODIPY-Based Near-Infrared Nanoparticles

Photothermal therapy (PTT) as a kind of noninvasive tumor treatment has attracted increasing research interest. However, the efficiency of existing PTT agents in the near-infrared (NIR) region is the major problem that has hindered further development of PTT. Herein, we present an effective strategy to construct the efficient photothermal agent by utilizing an intramolecular photoinduced electron transfer (PeT) mechanism, which is able to dramatically improve photothermal conversion efficiency in the NIR region. Specifically, an NIR dye (A1) constructed with dimethylamine moiety as the electron donor and the aza-BODIPY core as the electron acceptor is designed and synthesized, which can be used as a class of imaging-guided PTT agents via intramolecular PeT. After encapsulation with biodegradable polymer DSPE–mPEG₅₀₀₀, nanophotothermal agents with a small size exhibit excellent water solubility, photostability, and long-time retention in tumor. Importantly, such nanoparticles exhibit excellent photothermal conversion efficiency of ～35.0%, and the PTT effect in vivo still remains very well even with a low dosage of 0.05 mg kg^–1 upon 808 nm NIR laser irradiation (0.5 W cm^–2). Therefore, this reasonable design via intramolecular PeT offers guidance to construct excellent photothermal agents and subsequently may provide a novel opportunity for future clinical cancer treatment.