Dipartimento di Biotecnologie e Bioscienze, Università di Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Ospedale L. Sacco, Via G. B. Grassi 74, 20157 Milano, Italy.
Nat Commun. 2016 Dec 19;7:13818. doi: 10.1038/ncomms13818.
Active targeting of nanoparticles to tumours can be achieved by conjugation with specific antibodies. Specific active targeting of the HER2 receptor is demonstrated in vitro and in vivo with a subcutaneous MCF-7 breast cancer mouse model with trastuzumab-functionalized gold nanoparticles. The number of attached antibodies per nanoparticle was precisely controlled in a way that each nanoparticle was conjugated with either exactly one or exactly two antibodies. As expected, in vitro we found a moderate increase in targeting efficiency of nanoparticles with two instead of just one antibody attached per nanoparticle. However, the in vivo data demonstrate that best effect is obtained for nanoparticles with only exactly one antibody. There is indication that this is based on a size-related effect. These results highlight the importance of precisely controlling the ligand density on the nanoparticle surface for optimizing active targeting, and that less antibodies can exhibit more effect.
通过与特定抗体缀合，可以实现纳米颗粒对肿瘤的主动靶向。用曲妥珠单抗功能化的金纳米颗粒在体外和体内皮下 MCF-7 乳腺癌小鼠模型中证明了对 HER2 受体的特异性主动靶向。通过精确控制每个纳米颗粒上附着的抗体数量，使每个纳米颗粒上连接的抗体数量精确地为一个或两个。正如预期的那样，我们在体外发现，与每个纳米颗粒仅连接一个抗体相比，连接两个抗体可使纳米颗粒的靶向效率适度增加。然而，体内数据表明，对于每个纳米颗粒仅连接一个抗体的纳米颗粒，效果最佳。有迹象表明，这是基于尺寸相关的效应。这些结果强调了精确控制纳米颗粒表面配体密度以优化主动靶向的重要性，并且较少的抗体可以表现出更大的效果。
