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近红外区域的抗菌光动力疗法:连接到π-扩展卟啉的靶向抗菌肽

Antibacterial Photodynamic Therapy in the Near-Infrared Region with a Targeting Antimicrobial Peptide Connected to a π-Extended Porphyrin.

作者信息

Gourlot Charly, Gosset Alexis, Glattard Elise, Aisenbrey Christopher, Rangasamy Sabarinathan, Rabineau Morgane, Ouk Tan-Sothea, Sol Vincent, Lavalle Philippe, Gourlaouen Christophe, Ventura Barbara, Bechinger Burkhard, Heitz Valérie

机构信息

Laboratoire de Synthèse des Assemblages Moléculaires Multifonctionnels, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg, 4, rue Blaise Pascal, 67000 Strasbourg, France.

Biophysique des membranes et RMN, Institut de Chimie de Strasbourg, CNRS/UMR 7177, Université de Strasbourg, 4, rue Blaise Pascal, 67000 Strasbourg, France.

出版信息

ACS Infect Dis. 2022 Aug 12;8(8):1509-1520. doi: 10.1021/acsinfecdis.2c00131. Epub 2022 Jul 27.

Abstract

The increase of antimicrobial resistance to conventional antibiotics is worldwide a major health problem that requires the development of new bactericidal strategies. Antimicrobial photodynamic therapy (a-PDT) that generates reactive oxygen species acting on multiple cellular targets is unlikely to induce bacterial resistance. This localized treatment requires, for safe and efficient treatment of nonsuperficial infections, a targeting photosensitizer excited in the near IR. To this end, a new conjugate consisting of an antimicrobial peptide linked to a π-extended porphyrin photosensitizer was designed for a-PDT. Upon irradiation at 720 nm, the conjugate has shown at micromolar concentration strong bactericidal action on both Gram-positive and Gram-negative bacteria. Moreover, this conjugate allows one to reach a low minimum bactericidal concentration with near IR excitation without inducing toxicity to skin cells.

摘要

在全球范围内,对抗传统抗生素的耐药性增加是一个重大的健康问题,需要开发新的杀菌策略。产生作用于多个细胞靶点的活性氧的抗菌光动力疗法(a-PDT)不太可能诱导细菌耐药性。对于非浅表感染的安全有效治疗,这种局部治疗需要一种在近红外区域被激发的靶向光敏剂。为此,设计了一种由与π-扩展卟啉光敏剂相连的抗菌肽组成的新型共轭物用于a-PDT。在720nm波长照射下,该共轭物在微摩尔浓度时对革兰氏阳性菌和革兰氏阴性菌均表现出强烈的杀菌作用。此外,这种共轭物能够在近红外激发下达到低最低杀菌浓度,同时不会对皮肤细胞产生毒性。

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