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通过 TdT 引发的聚-G-四链体实现细胞表面受体和肿瘤靶向光动力治疗的同步监测。

Simultaneous Monitoring of Cell-surface Receptor and Tumor-targeted Photodynamic Therapy via TdT-initiated Poly-G-Quadruplexes.

机构信息

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, College of Chemistry and Chemical Engineering, Hunan University, Changsha, 410082, P. R. China.

出版信息

Sci Rep. 2018 Apr 3;8(1):5551. doi: 10.1038/s41598-018-23902-5.

DOI:10.1038/s41598-018-23902-5
PMID:29615769
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5882647/
Abstract

Cancer cells contain a unique set of cell surface receptors that provide potential targets for tumor theranostics. Here, we propose an efficient approach to construct G-quadruplex-based aptamers that specifically recognize cell-surface receptors and monitor them in an amplified manner. This designed aptamer combined particular sequence for the c-Met on the cell surface and poly-G-quadruplexes structures that allow a rapid and amplified fluorescent readout upon the binding of thioflavin T (ThT). The poly-G-quadruplexes also function as a carrier for photosensitizers such as TMPyP4 in that, the aptamer further trigger the production of reactive oxygen species (ROS) to commit cells to death. This unique c-Met targeting aptamer enabled simultaneous monitoring of c-Met on the cell surface with ThT and photodynamic killing of these lung cancer cells with TMPyP4. This strategy is expected to enhance the development of tumor-targeted diagnosis and drug delivery.

摘要

癌细胞含有一组独特的细胞表面受体,为肿瘤治疗学提供了潜在的靶点。在这里,我们提出了一种有效的方法来构建基于 G-四链体的适体,这些适体能够特异性识别细胞表面受体,并以放大的方式对其进行监测。这种设计的适体结合了细胞表面 c-Met 上的特定序列和聚 G-四链体结构,使得在结合硫黄素 T(ThT)时能够快速和放大荧光读数。聚 G-四链体还可以作为光敏剂如 TMPyP4 的载体,因为适体进一步触发活性氧(ROS)的产生,使细胞死亡。这种独特的 c-Met 靶向适体能够同时用 ThT 监测细胞表面上的 c-Met,并利用 TMPyP4 进行光动力杀伤这些肺癌细胞。该策略有望促进肿瘤靶向诊断和药物输送的发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/6374b4d78ba5/41598_2018_23902_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/fa8ed0697069/41598_2018_23902_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/9a8b511a5829/41598_2018_23902_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/7cfd017f1222/41598_2018_23902_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/a0e95a77e413/41598_2018_23902_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/1b718fc38f86/41598_2018_23902_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/6374b4d78ba5/41598_2018_23902_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/fa8ed0697069/41598_2018_23902_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/9a8b511a5829/41598_2018_23902_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/7cfd017f1222/41598_2018_23902_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/a0e95a77e413/41598_2018_23902_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/1b718fc38f86/41598_2018_23902_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e9fe/5882647/6374b4d78ba5/41598_2018_23902_Fig6_HTML.jpg

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