M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer.

M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer.
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DOI:
10.1038/nnano.2012.146
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发表时间:
2012-10
影响因子:
38.3
通讯作者:
--
中科院分区:
材料科学1区
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--
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分子成像允许临床医生可视化肿瘤的进展,并获取相关信息以进行患者诊断和治疗。由于其内在的光学,电气和磁性特性,纳米颗粒是成像动态分子和细胞过程(例如蛋白质 - 蛋白质相互作用,酶活性或基因表达)的有希望的对比剂。到目前为止,纳米颗粒已经通过靶向配体(例如抗体和肽)来改善肿瘤特异性和摄取的肽进行了设计。但是,配体的过度负荷可以降低配体的靶向能力,并降低纳米颗粒与细胞上有限数量的受体结合的能力。通过每个靶向分子增加传递到细胞的纳米颗粒的数量将导致较高的信噪比并改善图像对比度。在这里,我们表明M13丝状噬菌体可以用作脚手架,以显示靶向配体和多个纳米颗粒,用于癌细胞和小鼠肿瘤的磁共振成像。单分散氧化铁磁性纳米颗粒沿M13涂层组装,其远端进行了设计,以显示靶向SPARC糖蛋白的肽,该肽在各种癌症中均过表达。与直接用靶肽官能化的纳米颗粒相比,我们的方法改善了对比度,因为每个靶向SPARC的分子都将大量纳米颗粒传递到细胞中。此外,靶向配体和纳米颗粒可以很容易地交换为其他人,使该平台对体内高通量筛选和分子检测有吸引力。
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 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.
DOI: 10.1038/380364a0
发表时间: 1996-03-28
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影响因子: 64.8
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期刊: The Journal of cell biology
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影响因子: 11.1
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