Yao Qian, Cao Fei, Lang Marion, Feng Chao, Meng Xiaotong, Zhang Yongzhe, Zhao Yan, Wang Xiu-Hong
Laboratory for Biomedical Photonics, Institute of Laser Engineering, Beijing University of Technology, Beijing, 100124, China.
J Mater Chem B. 2017 Jul 14;5(26):5165-5175. doi: 10.1039/c7tb00152e. Epub 2017 Jun 14.
Antibody therapy is a type of immunotherapy that uses monoclonal antibodies (mAbs) to specifically bind to target cells to fight cancer. These mAbs have been conjugated with a number of nanocarriers to realize the targeted delivery of chemotherapeutics. Previous data indicate that the conjugation of a mAb to a nanocarrier promoted the faster internalization (endocytosis) of the nanoconjugates. In this study, we report that the crosslinking of Rituxan, an anti-lymphoma mAb, with silver nanoparticles prevented Rituxan from entering cells and prolonged drug/cell interaction. This finding was confirmed by both imaging flow cytometric and laser scanning confocal microscopic analyses of the fluorescently labeled nanoconjugates and cells. Furthermore, nanoconjugated Rituxan resulted in the enhanced capping of CD20 molecules on the cell membrane. We were able to show that the prolonged drug/cell interaction and enhanced capping directly contributed towards improved therapeutic efficiency. This represents a significant finding indicating that the nanocarrier served not only as a simple platform for targeted delivery, but also markedly altered the antibody performance at the molecular level and mediated key biological functions. The nanoconjugates also served as a Raman probe to specifically detect single live lymphoma cells with high sensitivity via surface-enhanced Raman scattering (SERS). Via integrating the single-cell level detection sensitivity of SERS with targeted and enhanced depletion ability, this nanoconjugate can be applied as a promising tool in lymphoma theranostics.
抗体疗法是一种免疫疗法，它利用单克隆抗体（mAb）特异性结合靶细胞来对抗癌症。这些单克隆抗体已与多种纳米载体偶联，以实现化疗药物的靶向递送。先前的数据表明，单克隆抗体与纳米载体的偶联促进了纳米偶联物更快地内化（内吞作用）。在本研究中，我们报告了抗淋巴瘤单克隆抗体利妥昔单抗（Rituxan）与银纳米颗粒交联后，阻止了利妥昔单抗进入细胞，并延长了药物/细胞相互作用。对荧光标记的纳米偶联物和细胞进行成像流式细胞术和激光扫描共聚焦显微镜分析，证实了这一发现。此外，纳米偶联的利妥昔单抗导致细胞膜上CD20分子的帽化增强。我们能够证明，延长的药物/细胞相互作用和增强的帽化直接有助于提高治疗效率。这是一个重要的发现，表明纳米载体不仅作为靶向递送的简单平台，而且在分子水平上显著改变了抗体性能并介导了关键的生物学功能。纳米偶联物还作为拉曼探针，通过表面增强拉曼散射（SERS）以高灵敏度特异性检测单个活淋巴瘤细胞。通过将SERS的单细胞水平检测灵敏度与靶向和增强的清除能力相结合，这种纳米偶联物可作为淋巴瘤诊疗的一种有前景的工具。
