Effect of charge localization on the in vivo optical imaging properties of near-infrared cyanine dye/monoclonal antibody conjugates.
Effect of charge localization on the in vivo optical imaging properties of near-infrared cyanine dye/monoclonal antibody conjugates.
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DOI：
10.1039/c6mb00371k
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发表时间：
2016-10-20
影响因子：
--
通讯作者：
Kobayashi H
中科院分区：
文献类型：
--
作者：
Sato K;Gorka AP;Nagaya T;Michie MS;Nakamura Y;Nani RR;Coble VL;Vasalatiy OV;Swenson RE;Choyke PL;Schnermann MJ;Kobayashi H
近红外（NIR）荧光团表现出比可见光荧光团更好的体内成像特性，因为这些波长的光在组织中的穿透性增加，而这些波长的自身荧光较低。我们最近报道了含有新型C4 ' - o -烷基连接剂的新型近红外菁染料，与现有的C4 ' - o -芳基变体相比，具有更高的化学稳定性和优异的光学性能。在本研究中，我们合成了两种核心结构和电荷相同但吲哚取代基不同的近红外菁染料：FNIR-Z-759携带两个磺酸盐和两个季铵阳离子的组合，FNIR-G-765携带两个磺酸盐和两个胍的组合，导致阳离子部分不同的两性离子电荷。在这项研究中，我们比较了FNIR-Z-759和FNIR-G-765单克隆抗体（mAb）偶联物与panitumumab （pan）在抗体-染料比为1:2或1:5时的体外和体内光学成像特性。pan- fnir - g -765的1 - 5共轭不成功，因为在共轭反应过程中形成聚集。两种染料与pan（2:1）的偶联物在体外靶细胞中表现出相似的猝灭能力、稳定性和亮度。然而，FNIR-Z-759偶联物在小鼠肝脏中的积累明显降低，导致更高的肿瘤-肝脏比率。因此，与FNIR-G-765偶联物相比，FNIR-Z-759偶联物似乎具有更好的体内成像特性，特别是在腹部区域。此外，从化学角度来看，与FNIR-Z-759偶联的mAb比FNIR-G-765有优势，因为它在高染料与mAb比时不会形成聚集体。这些结果表明，两性离子花青素染料是一类优越的荧光基团，可与单克隆抗体偶联，用于荧光成像应用，因为它可以提高体内目标与背景的对比度。然而，两性离子花青素染料应该仔细设计，因为结构的微小变化会改变单克隆抗体染料偶联物的体内药代动力学。两性离子cy7基菁染料化学结构的微小变化可以改变mab -染料偶联物的体内药代动力学。
Near-infrared (NIR) fluorophores show superior in vivo imaging properties than visible-light fluorophores because of the increased light penetration in tissue and lower autofluorescence of these wavelengths. We have recently reported that new NIR cyanine dyes containing a novel C4′-O-alkyl linker exhibit greater chemical stability and excellent optical properties relative to existing C4′-O-aryl variants. In this study, we synthesized two NIR cyanine dyes with the same core structure and charge but different indolenine substituents: FNIR-Z-759 bearing a combination of two sulfonates and two quaternary ammonium cations, and FNIR-G-765 bearing a combination of two sulfonates and two guanidines, resulting in zwitterionic charge with distinct cationic moieties. In this study, we compare the in vitro and in vivo optical imaging properties of monoclonal antibody (mAb) conjugates of FNIR-Z-759 and FNIR-G-765 with panitumumab (pan) at antibody-to-dye ratios of 1:2 or 1:5. One-to-five conjugation of pan-to-FNIR-G-765 was not successful due to aggregate formation during the conjugation reaction. Conjugates of both dyes to pan (2:1) demonstrated similar quenching capacity, stability, and brightness in target cells in vitro. However, FNIR-Z-759 conjugates showed significantly lower accumulation in the mouse liver, resulting in higher tumor-to-liver ratio. Thus, FNIR-Z-759 conjugates appear to have superior in vivo imaging characteristics compared with FNIR-G-765 conjugates, especially in the abdominal region. Moreover, from a chemistry point of view, mAb conjugation with FNIR-Z-759 has an advantage over FNIR-G-765, because it does not form aggregates at high dye-to-mAb ratio. These results suggest that zwitterionic cyanine dyes are a superior class of fluorophores for conjugating with mAbs for fluorescence imaging applications due to improving target-to-background contrast in vivo. However, zwitterionic cyanine dyes should be designed carefully, as small changes to the structure can alter in vivo pharmacokinetics of mAb-dye conjugates. Small changes on zwitterionic Cy7-based cyanine dyes to the chemical structure can alter in vivo pharmacokinetics of mAb-dye conjugates.
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影响因子：
6.4
作者：
Yano S;Hiroshima Y;Maawy A;Kishimoto H;Suetsugu A;Miwa S;Toneri M;Yamamoto M;Katz MH;Fleming JB;Urata Y;Tazawa H;Kagawa S;Bouvet M;Fujiwara T;Hoffman RM
通讯作者：
Hoffman RM
影响因子：
4.7
作者：
Sato K;Gorka AP;Nagaya T;Michie MS;Nani RR;Nakamura Y;Coble VL;Vasalatiy OV;Swenson RE;Choyke PL;Schnermann MJ;Kobayashi H
通讯作者：
Kobayashi H
影响因子：
9.7
作者：
Sato K;Nagaya T;Mitsunaga M;Choyke PL;Kobayashi H
通讯作者：
Kobayashi H
基于物理和生物学的下一代分子成像探针的合理化学设计：混合方式，颜色和信号。
影响因子：
46.2
作者：
Kobayashi H;Longmire MR;Ogawa M;Choyke PL
通讯作者：
Choyke PL
影响因子：
4.7
作者：
Toutchkine, Alexei;Nguyen, Dan-Vinh;Hahn, Klaus M.
通讯作者：
Hahn, Klaus M.