Thiophene Donor for NIR-II Fluorescence Imaging Guided Photothermal/Photodynamic/Chemo Combination Therapy

Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared windows. However, their applications in the second near-infrared (NIR-II) windows are still limited primarily owing to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) as the molecularly engineered thiophene donor unit with high QYs to the redshift is created. Thiophene insertion initiates substantial redshifts of the absorbance, as compared to its counterparts that introduce iodine. The fluorescent molecule can be triggered by a NIR laser with a single wavelength, producing emission in the NIR-II windows. Single NIR laser triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and chemotherapy drug docetaxel (DTX) using a synthetical amphiphilic poly(styrene- co -chloromethyl styrene)-graft-poly(ethylene glycol) functionalized with folic acid (FA). These BDP-T-N-DTX-FA NPs not only show superior solubility and high singlet oxygen quantum yield (ΦΔ =62%), but also demonstrate a single NIR laser-triggered multifunctional characteristics. After intravenous injection of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor presented a high signal-to-background ratio (11.8). Furthermore, the 4T1 tumors in mice were almost eradicated by released DTX and PDT/PTT combination therapy from the BDP-T-N-DTX-FA NPs under the single NIR laser excitation.