Abstract
It is always a huge challenge to develop novel near-infrared (NIR) phototherapeutic agents suitable for imaging-guided cancer therapy. In order to clarify the positive heavy atom effects on the photodynamic and photothermal efficiencies of phototherapeutic agents, a series of chlorine-, bromide-, or iodine-substituted aza-BODIPYs (B2, B3, and B4, respectively) are designed and synthesized. Among them, B4 exhibits both excellent photodynamic and photothermal effects (singlet oxygen yield of B4 is 1.57 times more than that of B3) and excellent photothermal effects (1.3 °C higher than that of B3). Then, nanoparticles of B4 (IABNs) with excellent biocompatibility are prepared by coating hydrophobic B4 with hydrophilic polymer DSPE-mPEG5000 . IABN exhibits high photostability, excellent biocompatibility, and low dark toxicity both in vivo and in vitro. Furthermore, IABN shows the enhanced photodynamic effect and high photothermal conversion efficiency (34.8%). In addition, the strong fluorescence emission of IABN makes it suitable for fluorescence imaging-guided tumor therapy in vivo. Finally, IABN has successfully healed the Hela tumor-bearing mice under NIR fluorescence imaging- and photothermal imaging-guided synergistic photothermal and photodynamic therapy with low side effects, demonstrating that it is promising for future clinical applications.
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