通过多光谱方法，研究壳聚糖基金纳米颗粒通过构象选择性与由短端粒DNA序列形成的平行G-四链体结合的抗癌治疗边缘。
Prospecting the cancer therapeutic edge of chitosan-based gold nanoparticles through conformation selective binding to the parallel G-quadruplex formed by short telomeric DNA sequence: A multi-spectroscopic approach.
发表日期：2023 Sep 12
作者：
Sonia, Shrikant Kukreti, Mahima Kaushik
来源：
Int J Biol Macromol
摘要：
在癌症治疗中，由端粒酶和癌基因启动子形成的G4结构的生物学相关性使其成为极其重要的治疗靶点。因此，我们通过绿色方法合成了以壳聚糖为基础的金纳米颗粒（CH-Au NPs），并研究了它们与由短端粒序列形成的G4结构的相互作用，以评估其针对G4结构的潜力。首先，我们使用光谱和生物物理技术表征了合成的CH-Au NPs的形态/物理属性以及模型G富集DNA序列12-mer d(T2G4)2 [TETRA]在盐依赖的结构方面。通过UV-Visible、CD、荧光、CD熔融、DLS和Zeta电位研究，评估了CH-Au NPs与平行/反平行TETRA G4结构之间的分子相互作用。实验数据表明，CH-Au NPs与平行TETRA G4表现出强烈的结合作用，并为其提供热稳定性，而与反平行TETRA G4 DNA和Ct-DNA（DNA双链）的相互作用几乎可以忽略。此外，我们还研究了CH-Au NPs对由人类端粒序列形成的不同G4结构（d(T2AG3)3 [HUM-12]和d(T2AG3)4T [HUM-25]）的选择性倾向性。我们的研究发现，CH-Au NPs表现出对G4结构的拓扑特异性结合能力，这可用于抑制/调节关键生物功能，具有潜在的抗癌活性。版权所有 © 2023. Elsevier B.V. 发表
The biological relevance of G4 structures formed in telomere & oncogenes promoters make them extremely crucial therapeutic target for cancer treatment. Herein, we have synthesized chitosan-based gold nanoparticles (CH-Au NPs) through green method and investigated their interaction with G4 structures formed by short telomeric sequences to evaluate their potential for targeting G4 structures. Firstly, we have characterized morphological/physical attributes of synthesized CH-Au NPs and salt dependent structural aspects of model G-rich DNA sequence, 12-mer d(T2G4)2 [TETRA] using spectroscopic and biophysical techniques. The molecular interactions between CH-Au NPs and parallel/antiparallel TETRA G4 structures were evaluated using UV-Visible, CD, Fluorescence, CD melting, DLS and Zeta potential studies. The experimental data indicate that CH-Au NPs show strong binding interactions with Parallel TETRA G4 and provide thermal stabilization to the structure whereas their interaction with Antiparallel TETRA G4 DNA and Ct-DNA (DNA duplex) were found to be negligible. Further, CH-Au NPs were also investigated for their selectivity aptitude for different G4 structures formed by human telomeric sequences; d(T2AG3)3 [HUM-12] and d(T2AG3)4T [HUM-25]. Our findings suggested that CH-Au NPs exhibit topology specific binding aptitude towards G4 structure which can be utilized to inhibit/modulate crucial biological functions for potential anticancer activity.Copyright © 2023. Published by Elsevier B.V.