Alves Fernanda, de Lima Isabelle Almeida, Fiuza Lorraine Gabriele, A Arnaut Zoe, Inada Natalia Mayumi, Bagnato Vanderlei Salvador
São Carlos Institute of Physics (IFSC), University of São Paulo (USP), São Carlos 13566-590, Brazil.
Department of Biomedical Engineering, Texas A&M University, College Station, TX 77843, USA.
Pathogens. 2025 Jun 21;14(7):618. doi: 10.3390/pathogens14070618.
is a Gram-negative, encapsulated bacterium recognized by the World Health Organization (WHO) as a critical priority for new therapeutic strategies due to its increasing multidrug resistance (MDR). Antimicrobial photodynamic therapy (aPDT) has emerged as a promising alternative to antibiotics, exhibiting a broad spectrum of action and multiple molecular targets, and has been proposed for the treatment of clinically relevant infections such as pneumonia. However, despite excellent in vitro photodynamic inactivation outcomes, the success of in vivo therapy still faces challenges, particularly due to the presence of lung surfactant (LS) in the alveoli. LS entraps photosensitizers, preventing these molecules from reaching microbial targets. This study investigated the potential of indocyanine green (ICG) in combination with the biocompatible polymer Gantrez™ AN-139 for the photoinactivation of . Initial in vitro experiments demonstrated that aPDT with ICG alone is effective against in a concentration- and light dose-dependent manner, achieving total eradication at 75 µg/mL of ICG and 150 J/cm of 808 nm light. When aPDT was performed with similar parameters in the presence of LS, no bacterial killing was observed. However, a significant synergistic effect was observed when ICG (25 µg/mL) was combined with a low concentration of Gantrez™ AN-139 (0.5% /) in the presence of dipalmitoylphosphatidylcholine (DPPC), the main component of LS. This formulation resulted in a substantial reduction (3.6 log) in viability. These findings highlight the potential of Gantrez™ AN-139 as an efficient carrier to enhance the efficacy of ICG-mediated aPDT against , even in the presence of lung surfactant, a necessary step before the in vivo experiments.
是一种革兰氏阴性、有荚膜的细菌，由于其日益增加的多重耐药性（MDR），被世界卫生组织（WHO）认定为新治疗策略的关键优先事项。抗菌光动力疗法（aPDT）已成为一种有前景的抗生素替代方法，具有广泛的作用谱和多个分子靶点，并已被提议用于治疗诸如肺炎等临床相关感染。然而，尽管在体外光动力灭活方面取得了优异的结果，但体内治疗的成功仍面临挑战，特别是由于肺泡中存在肺表面活性剂（LS）。LS会捕获光敏剂，阻止这些分子到达微生物靶点。本研究调查了吲哚菁绿（ICG）与生物相容性聚合物Gantrez™ AN - 139联合用于对 进行光灭活的潜力。最初的体外实验表明，单独使用ICG的aPDT以浓度和光剂量依赖的方式对 有效，在75 µg/mL的ICG和150 J/cm的808 nm光照射下可实现完全根除。当在存在LS的情况下以类似参数进行aPDT时，未观察到细菌杀灭。然而，当ICG（25 µg/mL）与低浓度的Gantrez™ AN - 139（0.5% /）在二棕榈酰磷脂酰胆碱（DPPC，LS的主要成分）存在下联合使用时，观察到了显著的协同效应。该制剂使 活力大幅降低（3.6个对数）。这些发现突出了Gantrez™ AN - 139作为一种有效载体的潜力，可增强ICG介导的aPDT对 的疗效，即使在存在肺表面活性剂的情况下也是如此，这是体内实验之前的必要步骤
