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载有替莫唑胺和 Cy7 的治疗诊断用 cRGD-BioShuttle 构建体用于近红外成像和治疗。

Theranostic cRGD-BioShuttle Constructs Containing Temozolomide- and Cy7 For NIR-Imaging and Therapy.

机构信息

1. DKFZ, Dept. of Imaging and Radiooncology, INF 280, D-69120 Heidelberg, Germany.

出版信息

Theranostics. 2011;1:381-94. doi: 10.7150/thno/v01p0381. Epub 2011 Dec 11.

DOI:10.7150/thno/v01p0381
PMID:22211144
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3248642/
Abstract

Innovative and personalized therapeutic approaches result from the identification and control of individual aberrantly expressed genes at the transcriptional and post-transcriptional level. Therefore, it is of high interest to establish diagnostic, therapeutic and theranostic strategies at these levels. In the present study, we used the Diels-Alder Reaction with inverse electron demand (DAR(inv)) click chemistry to prepare a series of cyclic RGD-BioShuttle constructs. These constructs carry the near-infrared (NIR) imaging agent Cy7 and the chemotherapeutic agent temozolomide (TMZ). We evaluated their uptake by and their efficacy against integrin α(v)β(3)-expressing MCF7 human breast carcinoma cells. In addition, using a mouse phantom, we analyzed the suitability of this targeted theranostic agent for NIR optical imaging. We observed that the cyclic RGD-based carriers containing TMZ and/or Cy7 were effectively taken up by α(v)β(3)-expressing cells, that they were more effective than free TMZ in inducing cell death, and that they could be quantitatively visualized using NIR fluorescence imaging. Therefore, these targeted theranostic agents are considered to be highly suitable systems for improving disease diagnosis and therapy.

摘要

创新和个性化的治疗方法源于在转录和转录后水平上识别和控制个体异常表达的基因。因此，在这些水平上建立诊断、治疗和治疗策略具有很高的兴趣。在本研究中，我们使用 Diels-Alder 反应与逆电子需求（DAR(inv)）点击化学来制备一系列环状 RGD-BioShuttle 构建体。这些构建体携带近红外（NIR）成像剂 Cy7 和化疗药物替莫唑胺（TMZ）。我们评估了它们对表达整合素 α(v)β(3)的 MCF7 人乳腺癌细胞的摄取和疗效。此外，我们使用小鼠体模分析了这种靶向治疗剂用于 NIR 光学成像的适用性。我们观察到，含有 TMZ 和/或 Cy7 的基于环状 RGD 的载体被表达 α(v)β(3)的细胞有效摄取，它们在诱导细胞死亡方面比游离 TMZ 更有效，并且可以使用 NIR 荧光成像进行定量可视化。因此，这些靶向治疗剂被认为是改善疾病诊断和治疗的高度合适的系统。

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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7864/3248642/2cd543880431/thnov01p0381g08.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7864/3248642/dd68eb4fbdf7/thnov01p0381g10.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7864/3248642/f599b11f4251/thnov01p0381g12.jpg

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