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连续靶向智能纳米探针用于转移性乳腺癌细胞质 microRNA 的分子识别。

Consecutive targetable smart nanoprobe for molecular recognition of cytoplasmic microRNA in metastatic breast cancer.

机构信息

Department of Chemical and Biomolecular Engineering, Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, Republic of Korea.

出版信息

ACS Nano. 2012 Oct 23;6(10):8525-35. doi: 10.1021/nn300289u. Epub 2012 Sep 7.

Abstract

We report smart nanoprobe, hyaluronic acid (HA)-based nanocontainers containing miR-34a beacons (bHNCs), for the intracellular recognition of miR-34a levels in metastatic breast cancer cells, which is distinct from the imaging of biomarkers such of cell membrane receptors such as HER2. In this study, we demonstrate that a nanoscale vesicle that couples a targeting endocytic route, CD44, and a molecular imaging probe enables the efficient detection of specific miRNAs. Furthermore, bHNCs showed no cytotoxicity and high stability due to the anchored HA molecules on the surface of nanocontainers, and enables the targeted delivery of beacons via CD44 receptor-mediated endocytosis. In vitro and in vivo optical imaging using bHNCs also allow the measurement of miR-34a expression levels due to the selective recognition of the beacons released from the internalized bHNCs. We believe that the technique described herein can be further developed as a cancer diagnostic as well as a miRNA-based therapy of metastatic cancer.

摘要

我们报告了一种智能纳米探针,即基于透明质酸(HA)的包含 miR-34a 探针的纳米容器(bHNCs),用于识别转移性乳腺癌细胞中的 miR-34a 水平,这与细胞膜受体等生物标志物的成像不同,如 HER2。在这项研究中,我们证明了一种纳米级囊泡,它结合了靶向内吞途径 CD44 和分子成像探针,能够高效检测特定的 miRNAs。此外,由于纳米容器表面锚定的 HA 分子,bHNCs 显示出无细胞毒性和高稳定性,并能够通过 CD44 受体介导的内吞作用靶向递送探针。使用 bHNCs 的体外和体内光学成像也允许测量 miR-34a 的表达水平,因为可以选择性地识别从内化的 bHNCs 中释放的探针。我们相信,本文所述的技术可以进一步发展为癌症诊断以及转移性癌症的 miRNA 治疗方法。

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