Molecular-level regulating intersystem crossing of polyphenols: Engineering high-efficiency phytochemical photosensitizer for MRSA elimination

IF 4.1 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Ting Du , Lizhi Liu , Shaochi Wang , Jianxing Feng , Linpin Luo , Liang Zhang , Xi Lan , Yizhong Shen , Shuo Shi , Jianlong Wang , Wentao Zhang
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引用次数: 0

Abstract

Natural polyphenols-mediated green photosterilization is promising but remains challenging in practical applications due to their unsatisfactory performance with insufficient intrinsic energy level and ROS generation. In this work, the molecular-level engineering strategy of natural polyphenols (quercetin, QC) by p-Methoxybezaldehyde (MB)-induced nucleophilic substitution is constructed for enhanced photodynamic MRSA therapy. Both the experimental and theoretical results disclose that the unprecedented H-aggregates of QC-MB supramolecular realized accelerated ISC with minimizing the energy level difference (ΔEst), achieving enhanced photodynamic performance with 2.2-fold enhancement on 1O2 quantum yield (75 %) compared to free quercetin (33 %). The well-designed photosensitizer realizes efficient MRSA elimination: with enhanced killing efficacy from 30.44 % to 99.95 % in vitro and effective eradication of mature biofilms. Mechanism study and gene transcription analysis reveal that the combined therapy of optical stimuli with QC-MB achieves the dual mechanism of ROS attack and virulence regulation against MRSA infection during the whole infection process. Moreover, the excellent biocompatibility and anti-infectious in vivo demonstrate the engineered QC-MB as a promising strategy for MRSA therapy.

调节多酚系统间交叉的分子水平:设计用于消除 MRSA 的高效植物化学光敏剂
天然多酚介导的绿色光固化技术前景广阔,但在实际应用中仍面临挑战,因为它们的内在能级和产生的 ROS 不尽人意。在这项工作中,通过对甲氧基苯甲醛(MB)诱导的亲核取代,构建了天然多酚(槲皮素,QC)的分子级工程策略,用于增强对 MRSA 的光动力治疗。实验和理论结果表明,QC-MB 超分子中前所未有的 H-聚集体在能级差(ΔEst)最小的情况下实现了加速 ISC,从而提高了光动力性能,与游离槲皮素(33%)相比,其 1O2 量子产率提高了 2.2 倍(75%)。这种精心设计的光敏剂能有效清除 MRSA:体外杀灭率从 30.44% 提高到 99.95%,并能有效根除成熟的生物膜。机理研究和基因转录分析表明,在整个感染过程中,光刺激与 QC-MB 的联合疗法实现了 ROS 攻击和毒力调控双重机制对 MRSA 感染的抑制。此外,工程化的 QC-MB 还具有良好的生物相容性和体内抗感染能力,是一种很有前景的 MRSA 治疗策略。
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来源期刊
ACS Chemical Neuroscience
ACS Chemical Neuroscience BIOCHEMISTRY & MOLECULAR BIOLOGY-CHEMISTRY, MEDICINAL
CiteScore
9.20
自引率
4.00%
发文量
323
审稿时长
1 months
期刊介绍: ACS Chemical Neuroscience publishes high-quality research articles and reviews that showcase chemical, quantitative biological, biophysical and bioengineering approaches to the understanding of the nervous system and to the development of new treatments for neurological disorders. Research in the journal focuses on aspects of chemical neurobiology and bio-neurochemistry such as the following: Neurotransmitters and receptors Neuropharmaceuticals and therapeutics Neural development—Plasticity, and degeneration Chemical, physical, and computational methods in neuroscience Neuronal diseases—basis, detection, and treatment Mechanism of aging, learning, memory and behavior Pain and sensory processing Neurotoxins Neuroscience-inspired bioengineering Development of methods in chemical neurobiology Neuroimaging agents and technologies Animal models for central nervous system diseases Behavioral research
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