HA-AuNPs/FDF用于透明质酸酶的高灵敏检测、肿瘤靶向细胞荧光成像和光疗  

HA-AuNPs/FDF for Highly Sensitive Detection of Hyaluronidase,Tumor-targeting Fluorescence Cell Imaging and Phototherapy

作　　者：黄艳琴[1] 栗丽君 杨书培 张瑞[1,3] 刘兴奋[1] 范曲立[1] 黄维[1,2] Huang Yanqin;Li Lijun;Yang Shupei;Zhang Rui;Liu Xingfen;Fan Qulia;Huang Wei(State Key Laboratory of Organic Electronics and Information Displays&Institute of Advanced Materials(IAM),Nanjing University of Posts&Telecommunications,Nanjing 210023,China;Shaanxi Institute of Flexible Electronics(SIFE),Northwestern Polytechnical University(NPU),Xi'an 710072,China;Department of Ophthalmology,Zhongda Hospital,Southeast University,Nanjing 210009,China)

机构地区：[1]南京邮电大学、有机电子与信息显示国家重点实验室、信息材料与纳米技术研究院,南京210023 [2]西北工业大学柔性电子研究院,西安710072 [3]东南大学附属中大医院眼科,南京210009

出　　处：《化学学报》2023年第12期1687-1694,共8页Acta Chimica Sinica

基　　金：江苏高校优势学科建设工程资助项目(YX03001);先进生物与化学制造国家协同创新中心及有机电子与信息显示国家重点实验室开放研究基金资助课题资助。

摘　　要：本工作构建了一种新型复合纳米诊疗剂HA-AuNPs/FDF,用于透明质酸酶(HAase)的高灵敏荧光检测、肿瘤靶向荧光成像和光动力/光热协同治疗.吡咯并吡咯二酮基共轭小分子(FDF)与肿瘤靶向生物分子透明质酸(HA)功能化的金纳米粒子(HA-AuNPs)通过静电作用自组装形成HA-Au NPs/FDF.FDF在近红外光激发下产生较强的荧光,HA-AuNPs会通过荧光共振能量转移效应(FRET)猝灭FDF的荧光.然而,肿瘤细胞中过表达的透明质酸酶(HAase)能使HA逐渐降解,FDF被释放,从而荧光逐渐恢复.HA-AuNPs/FDF的荧光恢复程度与HAase的浓度有很好的线性关系,可用于快速定量检测HAase.而且,HA-AuNPs/FDF作为透明质酸酶激活的荧光探针成功地用于人宫颈癌肿瘤HeLa细胞的靶向荧光成像,细胞实验结果证实它能通过光动力/光热协同治疗有效抑制HeLa细胞的增殖.该体系为实现精准高效的肿瘤诊疗拓展了思路.In this paper,a novel composite nano diagnostic and therapeutic agent HA-AuNPs/FDF was constructed for highly sensitive fluorescence detection of hyaluronidase(HAase),tumor-targeting fluorescence cell imaging and photodynamic/photothermal synergistic therapy.HA-AuNPs/FDF was formed by the electrostatic self-assembly of FDF,a diketopyrrolopyrrole-based conjugated small molecule,and HA-AuNPs,the gold nanoparticles functionalized with the tumor-targeting biomolecule hyaluronan(HA).FDF generated strong fluorescence under the excitation of near-infrared(NIR)light,and HA-AuNPs will quench the fluorescence of FDF through fluorescence resonance energy transfer(FRET).However,the overexpression of hyaluronidase(HAase)in tumor cells can gradually degrade HA,so FDF was released and the fluorescence of FDF was gradually recovered.Therefore,the fluorescence recovery of HA-AuNPs/FDF can be used for the rapid quantification of HAase.Experiments have shown that this method can achieve good linear response within the range of 0.25~2.25 U/mL with a detection limit of 0.04 U/mL.On this basis,after respective incubation with HA-AuNPs/FDF for 4 h,NIR fluorescence imaging was performed on human cervical cancer tumor cells(HeLa cells),HeLa cells pretreated with HA,and mouse embryonic fibroblasts(NIH-3T3 cells)to study the tumor-targeting capability of HA-AuNPs/FDF.In addition,after incubation with HA-AuNPs/FDF for 20 min,NIR fluorescence imaging was also performed on HeLa cells to detect the changes in fluorescence intensity over time and study the capability of HAase to activate fluorescence.All the results showed that HA-AuNPs/FDF was readily endocytosed by HeLa cells via the receptor CD44 and degraded by intracellular overexpressed HAase,and that it can be successfully used as a fluorescence probe activated by HAase for fluorescence cell imaging of HeLa cells.Furthermore,as FDF is a material with photothermal and photodynamic therapeutic potential,HA-AuNPs/FDF exhibited the single linear oxygen yield of 23.7%,with a photothermal conv

关 键 词：吡咯并吡咯二酮 纳米诊疗剂 透明质酸酶 荧光成像 光疗 

分 类 号：O657.3[理学—分析化学] R73[理学—化学]