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控制碳纳米管对化疗药物溶剂化颜色响应

Control of Carbon Nanotube Solvatochromic Response to Chemotherapeutic Agents.

机构信息

Memorial Sloan Kettering Cancer Center , New York, New York 10065, United States.

Weill Cornell Medical College, Cornell University , New York, New York 10065, United States.

出版信息

ACS Appl Mater Interfaces. 2017 Nov 1;9(43):37947-37953. doi: 10.1021/acsami.7b12015. Epub 2017 Oct 19.

Abstract

Alkylating agents such as cisplatin play an essential role in chemotherapy regimens, but initial and acquired resistance in many cancer types often dampen therapeutic response. The poor understanding of the mechanisms of resistance highlight the need for quantitative measurements of alkylating agent distribution at both the tissue and subcellular levels. Sensors for use in live animals and cells would allow for more effective study of drug action and resistance. Toward this end, single-walled carbon nanotubes suspended with single-stranded DNA have suitable optical properties for in vivo sensors, such as near-infrared emission and sensitivity to the local environment via solvatochromic responses. Currently, solvatochromic changes of such sensors have been limited by the chemical nature of the analyte, making it impossible to control the direction of energy emission changes. Here, we describe a new approach to control the direction and magnitude of solvatochromic responses of carbon nanotubes. We found that the alkylation of DNA on the nanotube surface can result in small changes in DNA conformation that allow the adsorption of amphiphiles to produce large differences (>14 nm) in response to different drugs. The technique surprisingly revealed differences among drugs upon alkylation. The ability to control carbon nanotube solvatochromism as desired may potentially expand the application of nanotube-based optical sensors for new classes of analytes.

摘要

烷化剂如顺铂在化疗方案中起着至关重要的作用,但许多癌症类型的初始和获得性耐药性常常削弱了治疗反应。对耐药机制的了解不足,突出了需要定量测量烷基化剂在组织和亚细胞水平上的分布。用于活体动物和细胞的传感器将允许更有效地研究药物作用和耐药性。为此,用单链 DNA 悬浮的单壁碳纳米管具有适合体内传感器的光学特性,例如近红外发射以及通过溶剂化响应对局部环境的敏感性。目前,这种传感器的溶剂化变化受到分析物化学性质的限制,使得无法控制能量发射变化的方向。在这里,我们描述了一种控制碳纳米管溶剂化响应方向和幅度的新方法。我们发现,纳米管表面上的 DNA 烷化可以导致 DNA 构象的微小变化,从而允许两亲物吸附,从而对不同的药物产生大的差异(>14nm)。该技术出人意料地揭示了烷基化后药物之间的差异。能够按需控制碳纳米管的溶剂化变色可能会潜在地扩展基于纳米管的光学传感器在新类分析物中的应用。

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