Nanobiophotonics and Laser Microspectroscopy Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, T Laurian 42, 400271, Cluj-Napoca, Romania.
Molecular Biology Center, Interdisciplinary Research Institute in Bio-Nano-Sciences, Babes-Bolyai University, T Laurian 42, 400271, Cluj-Napoca, Romania.
Colloids Surf B Biointerfaces. 2021 Jul;203:111755. doi: 10.1016/j.colsurfb.2021.111755. Epub 2021 Apr 8.
Herein, we report the fabrication of a nanotherapeutic platform integrating near-infrared (NIR) imaging with combined therapeutic potential through photodynamic (PDT) and photothermal therapies (PTT) and recognition functionality against ovarian cancer. Owing to its NIR fluorescence, singlet oxygen generation and heating capacity, IR780 iodide is exploited to construct a multifunctional nanosystem for single-wavelength NIR laser imaging-assisted dual-modal phototherapy. We opted for loading IR780 into polymeric Pluronic-F127-chitosan nanoformulation in order to overcome its hydrophobicity and toxicity and to allow functionalization with folic acid. The obtained nanocapsules show temperature-dependent swelling and spectroscopic behavior with favorable size distribution for cellular uptake at physiological temperatures, improved fluorescence properties and good stability. The fabricated nanocapsules can efficiently generate singlet oxygen in solution and are able to produce considerable temperature increase (46 °C) upon NIR laser irradiation. Viability assays on NIH-OVCAR-3 cells confirm the successful biocompatibilization of IR780 by encapsulating in Pluronic and chitosan polymers. NIR fluorescence imaging assays reveal the ability of folic-acid functionalized nanocapsules to serve as intracellular contrast agents and demonstrate their active targeting capacity against folate receptor expressing ovarian cancer cells (NIH-OVCAR-3). Consequently, the targeted nanocapsules show improved NIR laser induced phototherapeutic performance against NIH-OVCAR-3 cells compared to free IR780. We anticipate that this class of nanocapsules holds great promise as theranostic agents for application in image-guided dual PDT-PTT and imaging assisted surgery of ovarian cancer.
在此，我们报告了一种纳米治疗平台的制造，该平台通过光动力（PDT）和光热疗法（PTT）以及对卵巢癌的识别功能，整合了近红外（NIR）成像和联合治疗潜力。由于其近红外荧光、单线态氧产生和加热能力，我们利用 IR780 碘化物构建了一种多功能纳米系统，用于单波长近红外激光成像辅助双模光疗。我们选择将 IR780 装载到聚合物 Pluronic-F127-壳聚糖纳米制剂中，以克服其疏水性和毒性，并允许其与叶酸功能化。所得纳米胶囊具有温度依赖性的溶胀和光谱行为，具有在生理温度下摄取细胞的良好的粒径分布、改善的荧光性质和良好的稳定性。所制备的纳米胶囊可以在溶液中有效地产生单线态氧，并能够在近红外激光照射下产生相当大的温度升高（46°C）。对 NIH-OVCAR-3 细胞的活力测定证实了通过将 IR780 封装在 Pluronic 和壳聚糖聚合物中成功实现了生物相容性。近红外荧光成像测定揭示了叶酸功能化纳米胶囊作为细胞内对比剂的能力，并证明了它们对表达叶酸受体的卵巢癌细胞（NIH-OVCAR-3）的主动靶向能力。因此，与游离 IR780 相比，靶向纳米胶囊在 NIH-OVCAR-3 细胞中表现出改善的近红外激光诱导光疗性能。我们预计，这类纳米胶囊作为治疗学药物具有很大的应用潜力，可用于卵巢癌的图像引导双重 PDT-PTT 和成像辅助手术。
