基于共轭聚合物的纳米粒子用于肿瘤的近红外二区荧光成像及光热治疗

To improve the quality of fluorescence imaging and effectiveness of photothermal therapy, We designed a novel conjugated-polymer (BDT-TTQ) with a narrow band gap for NIR-II fluorescence and NIR-II photothermal effect. To realize solubility of BDT-TTQ in water, we enveloped the hydrophobic polymer BDT-TTQ into amphiphilic copolymer (PEG-b-PPG-b-PEG, F-127) shells for NIR-II water-soluble nanoparticles (BDT-TTQ NPs) through the nanoprecipitation method. With strong absorption in the NIR-II region of 1000 − 1200 nm, the BDT-TTQ NPs can realize fluorescence image during 1200 − 1400 nm excited by 1064 nm laser. The prepared BDT-TTQ NPs were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The average hydrodynamic radius of BDT-TTQ NPs was around 62 nm and spherical morphology was observed from TEM. Besides, the BDT-TTQ NPs showed the similar hydrodynamic radius in physiological environment such as phosphate buffer saline (PBS), Dulbecco's Modified Eagle Medium (DMEM) and fetal bovine serum (FBS) and exhibited the excellent biological stability, indicating the potential for further in vivo application. To study the NIR-II fluorescence characters, we firstly detected the maximum imaging depth of BDT-TTQ NPs in vitro and the penetration depth can achieve 6 mm at 1064 nm laser. High-resolution NIR-II fluorescence imaging of living blood vessels in mice was also achieved by BDT-TTO NPs under 1064 nm laser irradiation. In addition, the real-time NIR-II images of brain and abdomen were obtained with an ultrahigh signal-to-background ratio. Photothermal experiments suggested the BDT-TTQ NPs exhibited excellent photothermal conversion and outstanding photothermla stability under 1064 nm excitation, which revealed the potential of BDT-TTQ NPs for photothermal therapy in vivo. MTT assay and confocal laser scanning microscopy (CLSM) were used to analyse photothermal treatment toward human cervical carcinoma (HeLa) cells in vitro and the results indicated the nanoparticles performed an effective photothermal inhibition at the cellular level under laser irradiation. Morever, BDT-TTQ NPs developed in this study can realize NIR-II fluorescence imaging-guided photothermal therapy in vivo at 1064 nm laser.