Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Nat Nanotechnol. 2012 Oct;7(10):677-82. doi: 10.1038/nnano.2012.146. Epub 2012 Sep 16.
Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.
分子成像使临床医生能够可视化肿瘤的进展，并获得用于患者诊断和治疗的相关信息。由于其固有光学、电学和磁学特性，纳米粒子是用于成像动态分子和细胞过程（如蛋白质-蛋白质相互作用、酶活性或基因表达）的有前途的造影剂。到目前为止，纳米粒子已经通过靶向配体（如抗体和肽）进行了工程化，以提高肿瘤特异性和摄取率。然而，配体的过度加载会降低配体的靶向能力，并降低纳米粒子与细胞上有限数量的受体结合的能力。通过每个靶向分子向细胞中递增多的纳米粒子，将导致更高的信噪比，并提高图像对比度。在这里，我们表明，M13 丝状噬菌体可用作支架，以显示靶向配体和多个纳米粒子，用于对癌细胞和小鼠肿瘤进行磁共振成像。单分散氧化铁磁性纳米粒子沿 M13 衣壳组装，其末端经过工程改造以显示靶向 SPARC 糖蛋白的肽，SPARC 糖蛋白在各种癌症中过度表达。与直接用靶向肽功能化的纳米粒子相比，我们的方法提高了对比度，因为每个靶向 SPARC 的分子将大量纳米粒子递送到细胞中。此外，还可以轻松地将靶向配体和纳米粒子交换为其他配体和纳米粒子，使该平台成为体内高通量筛选和分子检测的有吸引力的选择。
