A Carbon Nanotube Optical Sensor Reports Nuclear Entry via a Noncanonical Pathway.
A Carbon Nanotube Optical Sensor Reports Nuclear Entry via a Noncanonical Pathway.
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DOI：
10.1021/acsnano.7b00176
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发表时间：
2017-04-25
期刊：
影响因子：
17.1
通讯作者：
Heller DA
中科院分区：
文献类型：
--
作者：
Budhathoki-Uprety J;Langenbacher RE;Jena PV;Roxbury D;Heller DA
单壁碳纳米管在生物医学成像和分子传感应用中很受关注，并且可以作为化疗药物、肽、蛋白质和寡核苷酸等各种货物的运输工具。碳纳米管表面化学可以调节用于亚细胞靶向，同时保留光致发光以在复杂的生物环境中进行无标记可视化，这使得它们成为此类研究的有吸引力的材料。细胞核是许多病理学的潜在靶标，包括癌症和传染病。了解纳米材料传递到细胞核的机制可能有助于诊断、药物开发和基因编辑工具。目前，还没有系统的研究来了解这些纳米材料如何进入细胞核。在此，我们开发了基于碳纳米管的杂化材料，阐明了纳米材料在培养细胞中核转位的独特机制。我们通过将光致发光单壁碳纳米管隐藏在胍功能化的螺旋聚碳二亚胺中，开发了一种核靶向纳米管。我们发现纳米管的核进入是由输入受体输入蛋白β介导的，无需输入蛋白α的帮助，而不是通过更常见的输入蛋白α/β途径。此外，纳米管光致发光在进入细胞核后表现出明显的红移，可能充当输入β介导的核运输过程的报告者。这项工作描绘了纳米材料递送至细胞核的非典型机制，并为细胞核相关病理学的研究提供了报告。
Single-walled carbon nanotubes are of interest in biomedicine for imaging and molecular sensing applications, and as shuttles for various cargos such as chemotherapeutic drugs, peptides, proteins, and oligonucleotides. Carbon nanotube surface chemistry can be modulated for subcellular targeting while preserving photoluminescence for label-free visualization in complex biological environments, making them attractive materials for such studies. The cell nucleus is a potential target for many pathologies including cancer and infectious diseases. Understanding mechanisms of nanomaterial delivery to the nucleus may facilitate diagnostics, drug development, and gene editing tools. Currently, there are no systematic studies to understand how these nanomaterials gain access to the nucleus. Herein, we developed carbon nanotube-based hybrid material which elucidated a distinct mechanism of nuclear translocation of a nanomaterial in cultured cells. We developed a nuclear-targeted nanotube via cloaking photoluminescent single-walled carbon nanotubes in a guanidinium-functionalized helical polycarbodiimide. We found that the nuclear entry of the nanotubes was mediated by the import receptor importin β without the aid of importin α and not by the more common importin α/β pathway. Additionally, the nanotube photoluminescence exhibited distinct red-shifting upon entry to the nucleus, potentially functioning as a reporter of the importin β-mediated nuclear transport process. This work delineates a non-canonical mechanism for nanomaterial delivery to the nucleus and provides a reporter for the study of nucleus-related pathologies.
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