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用于神经递质释放的光响应钌配合物的设计与评估:合成、表征、密度泛函理论及基因调控研究

Design and evaluation of light-responsive ruthenium complexes for neurotransmitter release: synthesis, characterization, DFT and gene regulation studies.

作者信息

Shah Naman, Karnik Rhydham, Shah Helly, Devkar Ranjitsinh V, Chakraborty Debjani

机构信息

Department of Chemistry, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390 002, India.

Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390 002, India.

出版信息

Photochem Photobiol Sci. 2025 Sep 17. doi: 10.1007/s43630-025-00777-w.

DOI:10.1007/s43630-025-00777-w
PMID:40960728
Abstract

Neurotransmitters are critical biomolecules involved in the mediation of synaptic transmission and the control of many neurophysiological processes. Their therapeutic potential, however, is usually limited by fast degradation, off-target action, and absence of spatial targeting. Photoactivated chemotherapy (PACT) offers a potential solution for spatially and temporally controlled delivery of bioactive molecules. In this paper, neurotransmitters were encapsulated in light-sensitive ruthenium (II) polypyridyl caged complexes, which would be inert in the dark and release upon irradiation with 465 nm blue light through photolysis. The complexes were prepared and thoroughly characterized by UV-VIS spectroscopy, FTIR, ESI-MS, NMR, CHNS elemental analysis, and ICP-MS, establishing coordination and structural integrity. Photorelease of neurotransmitters was verified by time-resolved UV-VIS and mass spectrometric investigations. To assess the biological relevance of light-induced release, gene expression analysis was conducted, demonstrating upregulation of the important neuronal markers after irradiation. The findings prove the efficiency of ruthenium-based cages in light-regulated neurotransmitter delivery and justify their possible application in neurotherapeutic PACT platforms.

摘要

神经递质是参与突触传递介导和许多神经生理过程控制的关键生物分子。然而,它们的治疗潜力通常受到快速降解、脱靶作用和缺乏空间靶向性的限制。光活化化疗(PACT)为生物活性分子的时空控制递送提供了一种潜在的解决方案。在本文中,神经递质被包裹在光敏钌(II)多吡啶笼状配合物中,这些配合物在黑暗中呈惰性,在465 nm蓝光照射下通过光解作用释放。通过紫外可见光谱、傅里叶变换红外光谱、电喷雾电离质谱、核磁共振、元素分析(CHNS)和电感耦合等离子体质谱对配合物进行了制备和全面表征,确定了其配位和结构完整性。通过时间分辨紫外可见光谱和质谱研究验证了神经递质的光释放。为了评估光诱导释放的生物学相关性,进行了基因表达分析,结果表明照射后重要神经元标志物上调。这些发现证明了钌基笼状配合物在光调控神经递质递送中的有效性,并证明了它们在神经治疗PACT平台中的潜在应用价值。

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