Department of Biomedical Engineering , The City College of New York , 160 Convent Avenue , New York , New York 10031 , United States.
Vascular Biology Program , Boston Children's Hospital , 300 Longwood Avenue , Boston , Massachusetts 02115 , United States.
Nano Lett. 2018 Apr 11;18(4):2254-2262. doi: 10.1021/acs.nanolett.7b04801. Epub 2018 Mar 12.
Atomic force microscopy (AFM) is a powerful tool to detect in vitro antibody-antigen interactions. To date, however, AFM-measured antibody-antigen interactions have yet to be exploited to predict in vivo tumor specificity of antibody-directed nanomedicines. In this study, we have utilized AFM to directly measure the biomechanical interaction between live triple negative breast cancer (TNBC) cells and an antibody against ICAM1, a recently identified TNBC target. For the first time, we provide proof-of-principle evidence that in vitro TNBC cell-ICAM1 antibody binding force measured by AFM on live cells more precisely correlates with in vivo tumor accumulation and therapeutic efficacy of ICAM1 antibody-directed liposomes than ICAM1 gene and surface protein overexpression levels. These studies demonstrate that live cell-antibody binding force measurements may be used as a novel in vitro metric for predicting the in vivo tumor recognition of antibody-directed nanomedicines.
原子力显微镜(AFM)是一种强大的工具,可用于检测体外抗体-抗原相互作用。然而,迄今为止,AFM 测量的抗体-抗原相互作用尚未被用于预测抗体导向纳米药物的体内肿瘤特异性。在这项研究中,我们利用 AFM 直接测量活三阴性乳腺癌(TNBC)细胞与针对 ICAM1 的抗体之间的生物力学相互作用,ICAM1 是最近确定的 TNBC 靶标。我们首次提供了原理证明证据,即在活细胞上通过 AFM 测量的体外 TNBC 细胞-ICAM1 抗体结合力与 ICAM1 抗体导向脂质体的体内肿瘤积累和治疗效果比 ICAM1 基因和表面蛋白过表达水平更精确相关。这些研究表明,活细胞-抗体结合力测量值可用作预测抗体导向纳米药物体内肿瘤识别的新型体外指标。