Zekun Gao, Xiuli Zheng, Xiangyu Dong, Weimin Liu, Jie Sha, Shuaishuai Bian, Jian Li, Huan Cong, Chun-Sing Lee, Pengfei Wang
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Specifically, AnBox·4Cl, a water-soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host-guest complexes with high binding constants (≈10<sup>7</sup> m <sup>-1</sup>) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram-negative bacteria. As a result, the AnBox·4Cl-PQPS complexes can effectively anchor on the surfaces of gram-negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad-spectrum PDAT effect against both gram-negative and gram-positive bacteria. 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引用次数: 0
摘要
过醌类天然产物是一类光敏剂(PSs),可产生大量活性氧(ROS),在 I 型/II 型双重光动力疗法中具有出色的活性。然而,它们对革兰氏阴性菌的活性有限,而且水溶性差,这大大限制了它们在广谱光动力抗菌疗法(PDAT)中的潜力。本文介绍了一种利用大环超分子载体克服过醌类光敏剂(PQPSs)在光动力抗菌疗法中的局限性的通用方法。具体来说,AnBox-4Cl(一种水溶性阳离子环烷)被确定为烯丙基喹啉色素 C、次喹啉色素 A、次喹啉色素 B 和金丝桃素等 PQPSs 的通用大环载体,可在水溶液中形成具有高结合常数(≈107 m -1 )的 1:1 主-客复合物。每个 AnBox-4Cl 分子都带有四个正电荷,可促进与革兰氏阴性细菌膜的强结合。因此,AnBox-4Cl-PQPS 复合物能有效地固定在革兰氏阴性细菌的表面,而单独的 PQPSs 则不能。体外和体内实验证明,这些超分子 PS 具有优异的水溶性和高 ROS 生成能力,对革兰氏阴性菌和革兰氏阳性菌都有广谱 PDAT 作用。这项工作展示了一种提高 PQPSs 水溶性和杀灭革兰氏阴性菌功效的有效方法,为增强 PDAT 铺平了新的道路。
A General Strategy for Enhanced Photodynamic Antimicrobial Therapy with Perylenequinonoid Photosensitizers Using a Macrocyclic Supramolecular Carrier.
Perylenequinonoid natural products are a class of photosensitizers (PSs) that exhibit high reactive oxygen species (ROS) generation and excellent activity for Type I/Type II dual photodynamic therapy. However, their limited activity against gram-negative bacteria and poor water solubility significantly restrict their potential in broad-spectrum photodynamic antimicrobial therapy (PDAT). Herein, a general approach to overcome the limitations of perylenequinonoid photosensitizers (PQPSs) in PDAT by utilizing a macrocyclic supramolecular carrier is presented. Specifically, AnBox·4Cl, a water-soluble cationic cyclophane, is identified as a universal macrocyclic host for PQPSs such as elsinochrome C, hypocrellin A, hypocrellin B, and hypericin, forming 1:1 host-guest complexes with high binding constants (≈107 m -1) in aqueous solutions. Each AnBox·4Cl molecule carries four positive charges that promote strong binding with the membrane of gram-negative bacteria. As a result, the AnBox·4Cl-PQPS complexes can effectively anchor on the surfaces of gram-negative bacteria, while the PQPSs alone cannot. In vitro and in vivo experiments demonstrate that these supramolecular PSs have excellent water solubility and high ROS generation, with broad-spectrum PDAT effect against both gram-negative and gram-positive bacteria. This work paves a new path to enhance PDAT by showcasing an efficient approach to improve PQPSs' water solubility and killing efficacy for gram-negative bacteria.
期刊介绍:
Advanced Healthcare Materials, a distinguished member of the esteemed Advanced portfolio, has been dedicated to disseminating cutting-edge research on materials, devices, and technologies for enhancing human well-being for over ten years. As a comprehensive journal, it encompasses a wide range of disciplines such as biomaterials, biointerfaces, nanomedicine and nanotechnology, tissue engineering, and regenerative medicine.