Artemisinin Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China; Department of Chemistry, Stanford University, CA 94305, United States.
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of TCM Evaluation and Translational Research, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 21198, China.
Acta Biomater. 2021 Jun;127:287-297. doi: 10.1016/j.actbio.2021.03.064. Epub 2021 Apr 6.
Organic fluorophores/photosensitizers have been widely used in biological imaging and photodynamic and photothermal combination therapy in the first near-infrared (NIR-I) window. However, their applications in the second near-infrared (NIR-II) window are still limited primarily due to low fluorescence quantum yields (QYs). Here, a boron dipyrromethene (BDP) is created as a molecularly engineered thiophene donor unit with high QYs to the redshift. Thiophene insertion initiates substantial redshifts of the absorbance as compared to its counterparts in which iodine is introduced. The fluorescent molecule can be triggered by an NIR laser with a single wavelength, thereby producing emission in the NIR-II windows. Single NIR laser-triggered phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and the chemotherapeutic drug docetaxel (DTX) by using a synthetic 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 QY (Φ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics. After intravenous administration of the NPs into 4T1 tumor-bearing mice, the accumulation of the NPs in the tumor showed a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the combination of photodynamic therapy (PDT) and photothermic therapy (PTT). STATEMENT OF SIGNIFICANCE: The application of organic photosensitizers is still limited primarily due to low fluorescence quantum yields (QYs) in the second near-infrared (NIR-II) window. Here, a boron dipyrromethene (BDP) as a molecularly engineered thiophene donor unit with high QYs to the redshift is created. Phototherapeutic nanoparticles (NPs) are developed by encapsulating the BDP and docetaxel (DTX) using a synthetic 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 high singlet oxygen QY (Φ=62%) but also demonstrate single NIR laser-triggered multifunctional characteristics and a high signal-to-background ratio (11.8). Furthermore, 4T1 tumors in mice were almost eradicated by DTX released from the BDP-T-N-DTX-FA NPs under single NIR laser excitation and the PDT/PTT combination therapy.
有机荧光团/光敏剂已广泛应用于第一近红外 (NIR-I) 窗口的生物成像和光动力和光热联合治疗。然而，由于荧光量子产率 (QY) 低，它们在第二近红外 (NIR-II) 窗口的应用仍然有限。在这里，创建了硼二吡咯甲川（BDP）作为一种分子工程噻吩供体单元，具有高 QY 到红移。与碘引入的同类物相比，噻吩的插入引发了吸收的显著红移。荧光分子可以被单波长的近红外激光触发，从而在近红外-II 窗口产生发射。通过使用合成的两亲性聚（苯乙烯-co-氯甲基苯乙烯）-接枝-聚（乙二醇）功能化叶酸（FA）来封装 BDP 和化疗药物多西他赛（DTX），开发出单近红外激光触发的光疗纳米颗粒（NPs）。BDP-T-N-DTX-FA NPs 不仅表现出优异的溶解度和高单线态氧 QY（Φ=62%），而且还表现出单近红外激光触发的多功能特性。将 NPs 静脉注射到 4T1 荷瘤小鼠后，肿瘤中 NPs 的积累显示出高信号与背景比（11.8）。此外，在单近红外激光激发和光动力疗法（PDT）和光热疗法（PTT）联合作用下，BDP-T-N-DTX-FA NPs 释放的 DTX 几乎可以消除 4T1 肿瘤。
