Bio-orthogonal Supramolecular Latching inside Live Animals and Its Application for in Vivo Cancer Imaging
Bio-orthogonal Supramolecular Latching inside Live Animals and Its Application for in Vivo Cancer Imaging
复制标题
DOI：
10.1021/acsami.9b16283
复制
发表时间：
2019-11-27
影响因子：
9.5
通讯作者：
Kim, Kimoon
中科院分区：
文献类型：
--
作者：
Li, Meng;Kim, Sungwan;Kim, Kimoon
在这里，我们展示了一种超分子锁定工具，用于在活体动物模型中生物正交非共价锚定小合成分子，使用完全合成的瓜bb[7] （CB[7]）和adamantylammonium （AdA）之间的高亲和力结合对。这种超分子锁存系统很小（类似于1kda），确保有效地吸收到细胞、组织和整个生物体中。它还具有化学稳定性和抗酶降解能力，在非共价结合方面类似于特性良好的生物系统。在秀丽隐杆线虫（Caenorhabditis elegans）体内，花青素3-CB[7] （Cy3-CB[7]）与硼-二吡啶630/650X-AdA （BDP630/650-AdA）之间发生荧光共振能量转移（FRET），表明AdA与CB[7]在活体动物体内存在高效的原位高亲和关联。此外，将Cy5-AdA （cyanine 5-AdA, Cy5-AdA）超分子锁定在癌症部位预定位的CB[7]偶联抗体上，对活体小鼠的癌症部位进行选择性可视化，证明了该合成系统在体内癌症成像方面的潜力。这些发现为开发新的化学生物学工具和医学治疗系统提供了新的见解。
Here, we demonstrate a supramolecular latching tool for bio-orthogonal noncovalent anchoring of small synthetic molecules in live animal models using a fully synthetic high-affinity binding pair between cucurbit[7]uril (CB[7]) and adamantylammonium (AdA). This supramolecular latching system is small (similar to 1 kDa), ensuring efficient uptake into cells, tissues, and whole organisms. It is also chemically robust and resistant to enzymatic degradation and analogous to well-characterized biological systems in terms of noncovalent binding. Occurrence of fluorescence resonance energy transfer (FRET) between cyanine 3-CB[7] (Cy3-CB[7]) and boron-dipyrromethene 630/650X-AdA (BDP630/650-AdA) inside a live worm (Caenorhabditis elegans) indicates efficient in situ high-affinity association between AdA and CB[7] inside live animals. In addition, selective visualization of a cancer site of a live mouse upon supramolecular latching of cyanine 5-AdA (Cy5-AdA) on prelocalized CB[7]-conjugating antibody on the cancer site demonstrates the potential of this synthetic system for in vivo cancer imaging. These findings provide a fresh insight into the development of new chemical biology tools and medical therapeutic systems.