Multicolor Raman Beads for Multiplexed Tumor Cell and Tissue Imaging and in Vivo Tumor Spectral Detection
Multicolor Raman Beads for Multiplexed Tumor Cell and Tissue Imaging and in Vivo Tumor Spectral Detection
复制标题
用于多重肿瘤细胞和组织成像以及体内肿瘤光谱检测的多色拉曼珠
DOI：
10.1021/acs.analchem.9b00028
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发表时间：
2019-03-19
影响因子：
7.4
通讯作者：
Tang, Xinjing
中科院分区：
文献类型：
--
作者：
Jin, QingQing;Fan, Xinli;Tang, Xinjing
开发在生物喇曼无声区(1800-2800 cm(-1))具有强烈而独特的喇曼振动的新型纳米材料非常适合于活细胞和动物的喇曼高光谱检测和成像。在本论文中，我们制备了单体含有炔烃、氰化物、叠氮化物和氢化碳的聚合物纳米粒子，作为生物成像用的拉曼活性纳米材料(拉曼珠)。在没有金属(如Au或Ag)作为拉曼增强剂的情况下，由于单个纳米粒子中含有高密度的炔烃、氰化物、叠氮化物和氢化碳，因此获得了强烈的拉曼信号。我们开发了一个用于通过单体末端封端取代进行频率多路复用的拉曼珠库，并展示了具有不同拉曼频率的混合纳米粒子的五色SRS成像。此外，随着靶向部分(如核酸适配子和靶向多肽)的进一步表面功能化，靶向拉曼小球被成功地用作肿瘤靶向和拉曼光谱检测的探针，包括在活的肿瘤细胞和组织中进行多色SRS成像，具有很高的特异性。进一步的体内研究表明，尾静脉注射后，锚定靶向部分的拉曼小球成功地靶向了活体小鼠的肿瘤，活体小鼠肿瘤的拉曼光谱检测只能通过生物拉曼无声区域的自发拉曼信号实现，由于拉曼小球中有高密度的拉曼报告，因此没有任何信号增强。随着这些单体的进一步共聚，可以很容易地获得具有超多路条形码的拉曼微珠。
Developing new nanomaterials with strong and distinctive Raman vibrations in the biological Raman-silent region (1800-2800 cm(-1)) were highly desirable for Raman hyperspectral detection and imaging in living cells and animals. Herein, polymeric nanoparticles with monomers containing alkyne, cyanide, azide, and carbon-deuterate were prepared as Raman-active nanomaterials (Raman beads) for bioimaging applications. Intense Raman signals were obtained due to the high density of alkyne, cyanide, azide, and carbon-deuterate in single nanoparticles, in absence of metal (such as Au or Ag) as Raman enhancers. We have developed a library of Raman beads for frequency multiplexing through the end capping substitutions of monomers and demonstrated five color SRS imaging of mixed nanoparticles with distinct Raman frequencies. In addition, with further surface functionalization of targeting moieties (such as nucleic acid aptamers and targeting peptides), targetable Raman beads were successfully used as probes for tumor targeting and Raman spectroscopic detection, including multicolor SRS imaging in living tumor cells and tissues with high specificity. Further in vivo studies indicated that Raman beads anchored with targeting moieties were successfully employed to target tumors in living mice after tail intravenous injection, and Raman spectral detection of tumor in live mice was achieved only through spontaneous Raman signal at the biological Raman-silent region without any signal enhancement due to a high density of Raman reporters in Raman beads. With further copolymerization of these monomers, Raman beads with supermultiplex barcoding could be readily achieved.