近红外二区荧光纳米探针的制备及其在生物成像中的应用  

Synthesis and Bioimaging Application of Near-infrared Ⅱ Fluorescence Nanoprobes

作　　者：彭锦雯[1] 杜肖龙 陈妍[2] 孙鹏飞[2] 邓卫星[1] 范曲立[2] Jin-wen Peng;Xiao-long Du;Yan Chen;Peng-fei Sun;Wei-xing Deng;Qu-li Fan(Key Laboratory of New Processing Technology for Nonferrous Metals and Materials,Guilin University of Technolog,Guilin 541004;Key Laboratory for Organic Electronics and Information Displays,Institute of Advanced Materials(IAM),Jiangsu Key Laboratory for Biosensors,Nanjing University of Posts&Telecommunications,Nanjing 210023)

机构地区：[1]桂林理工大学有色金属及材料加工新技术教育部重点实验室,桂林541004 [2]南京邮电大学有机电子与信息显示国家重点实验室培育基地信息材料与纳米技术研究院江苏省生物传感材料与技术重点实验室,南京210023

出　　处：《高分子学报》2020年第11期1275-1284,I0005,共11页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号21864010);广西省自然科学基金(基金号2018GXNSFAA050030)资助项目.

摘　　要：通过Stille交叉偶联反应制备了一种具有供体-受体(D-A)结构的低能带隙共轭聚合物(pTB),并应用于小鼠的NIR-II生物成像.为了改善聚合物材料的水溶性和生物相容性,采用纳米沉积技术引入二硬脂酰磷脂酰乙酰胺-甲氧基聚乙二醇(DSPE-mPEG),合成了稳定的聚合物纳米粒子(pTB-PEG).通过核磁共振氢谱(1H-NMR)、紫外-可见-近红外吸收光谱(UV-Vis)、动态光散射(DLS)、透射电子显微镜(TEM)等测试对其结构、性能和形貌进行了表征分析,结果显示该共轭聚合物纳米颗粒在831 nm处有良好的吸收峰,具有206 nm的大斯托克斯(Stokes)位移;此外,该纳米粒子不但具备优良的光稳定性和良好的生物相容性,体外细胞的荧光共聚焦成像实验研究结果进一步表明这种粒子还具备良好的的光热治疗性能.更重要的是,由于该共轭聚合物的高发射(>1000 nm)特性,其成像深度为6 mm,远远超过了传统的近红外一区(NIR-I)试剂,并且有效地实现了对健康小鼠血管系统和荷瘤小鼠的的近红外二区(NIR-II)荧光成像.总体而言,共轭聚合物纳米粒子(pTB-PEG)具备杰出的生物相容性、优异的光稳定性和良好的光学功能,是一种极具前景的NIR-II成像探针,具备广泛应用于临床成像和活体肿瘤成像的潜力.Fluorescence imaging in the second near-infrared window(NIR-II)holds promise for real-time deep tissue imaging.In this work,we design a low-band gap conjugated polymers(pTB)with donor-acceptor(D-A)structures by Stille cross-coupling reaction,which can improve the quality of fluorescence imaging and effectiveness of photothermal therapy.In order to improve the water solubility and biocompatibility of pTB,we adopted nano-deposition technology to envelop the hydrophobic polymer pTB into amphiphilic copolymer(1,2-distearoyl-phosphatidylethanolamine-methyl-polyethyleneglycol conjugate(DSPE-mPEG))shells for NIR-II water-soluble nanoparticles(pTB-PEG).The structure,properties and morphology of the polymer were analyzed by 1H-NMR,UV-Vis,dynamic light scattering(DLS)and transmission electron microscopy(TEM).The results show that the conjugated polymer nanoparticles have not only a good absorption peak at 831 nm,but also a large Stokes shift of 206 nm.In addition,the average hydrodynamic radius of pTB-PEG NPs was around 69 nm and spherical morphology was observed from TEM.And the nanoparticles also possess excellent photostability and good biocompatibility in physiological environment such as phosphate buffer saline(PBS),Dulbecco's Modified Eagle Medium(DMEM)and fetal bovine serum(FBS),indicating the potential for further in vivo application.More importantly,we used MTT assay to analyze photothermal treatment toward human breast cancer(4T1)cells in vitro,and confocal laser scanning microscopy(CLSM)tests further indicated that this material has a good photothermal therapeutic effect.To study the NIR-II fluorescence characters,we firstly detected the maximum imaging depth of pTB-PEG NPs in vitro.With the help of long-wavelength emission(>1000 nm),the imaging depth is 6 mm,far exceeding the traditional near-infrared region(NIR-I)reagents.Under 808 nm laser irradiation,the high-resolution second near-infrared window(NIR-II)fluorescence imaging of healthy mouses’blood vascular system and tumor-bearing mice was effectively ach

关 键 词：共轭聚合物 光热治疗性能 血管系统 近红外二区荧光成像 

分 类 号：R318[医药卫生—生物医学工程] O657.3[医药卫生—基础医学]