Prieto-Montero Ruth, Herrera Lucia, Tejón Maite, Albaya Andrea, Chiara Jose Luis, Fanarraga Mónica L, Martínez-Martínez Virginia
Departamento de Química Física, Facultad de Ciencia y Tecnología, Universidad del País Vasco, UPV-EHU, Apartado 644, 48080 Bilbao, Spain.
Instituto de Química Orgánica General (IQOG-CSIC), Juan de la Cierva 3, 28006 Madrid, Spain.
Nanomaterials (Basel). 2024 Dec 11;14(24):1982. doi: 10.3390/nano14241982.
Antimicrobial resistance (AMR), a consequence of the ability of microorganisms, especially bacteria, to develop resistance against conventional antibiotics, hampering the treatment of common infections, is recognized as one of the most imperative health threats of this century. Antibacterial photodynamic therapy (aPDT) has emerged as a promising alternative strategy, utilizing photosensitizers activated by light to generate reactive oxygen species (ROS) that kill pathogens without inducing resistance. In this work, we synthesized silica nanoparticles (NPs) of different sizes (20 nm, 80 nm, and 250 nm) functionalized with the photosensitizer Rose Bengal (RB) and a gluconamide ligand, which targets Gram-negative bacteria, to assess their potential in aPDT. Comprehensive characterization, including dynamic light scattering (DLS) and photophysical analysis, confirmed the stability and effective singlet oxygen production of the functionalized nanoparticles. Although the surface loading density of Rose Bengal was constant at the nanoparticle external surface, RB loading (in mg/g nanoparticle) was size-dependent, decreasing with increasing nanoparticle diameter. Further, the spherical geometry of nanoparticles favored smaller nanoparticles for antibacterial PDT, as this maximizes the surface contact area with the bacteria wall, with the smallest (20 nm) and intermediate (80 nm) particles being more promising. Bacterial assays in revealed minimal dark toxicity and significant light-activated phototoxicity for the RB-loaded nanoparticles. The addition of gluconamide notably enhanced phototoxic activity, particularly in the smallest nanoparticles (RB-G-20@SiNP), which demonstrated the highest phototoxicity-to-cytotoxicity ratio. These findings indicate that small, gluconamide-functionalized silica nanoparticles are highly effective for targeted aPDT, offering a robust strategy to combat AMR.
抗菌耐药性（AMR）是微生物，尤其是细菌对传统抗生素产生耐药性的结果，它阻碍了常见感染的治疗，被认为是本世纪最紧迫的健康威胁之一。抗菌光动力疗法（aPDT）已成为一种有前景的替代策略，它利用光激活的光敏剂产生活性氧（ROS）来杀死病原体而不诱导耐药性。在这项工作中，我们合成了不同尺寸（20纳米、80纳米和250纳米）的二氧化硅纳米颗粒（NPs），这些纳米颗粒用光敏剂孟加拉玫瑰红（RB）和一种靶向革兰氏阴性菌的葡糖酰胺配体进行了功能化，以评估它们在aPDT中的潜力。包括动态光散射（DLS）和光物理分析在内的全面表征证实了功能化纳米颗粒的稳定性和有效的单线态氧产生。尽管孟加拉玫瑰红在纳米颗粒外表面的表面负载密度是恒定的，但RB负载量（以毫克/克纳米颗粒计）与尺寸有关，随着纳米颗粒直径的增加而降低。此外，纳米颗粒的球形几何形状有利于较小的纳米颗粒用于抗菌光动力疗法，因为这最大化了与细菌细胞壁的表面接触面积，最小的（20纳米）和中等大小的（80纳米）颗粒更有前景。细菌试验表明，负载RB的纳米颗粒具有最小的暗毒性和显著的光激活光毒性。葡糖酰胺的加入显著增强了光毒性活性，特别是在最小的纳米颗粒（RB-G-20@SiNP）中，其表现出最高的光毒性与细胞毒性之比。这些发现表明，小的、葡糖酰胺功能化的二氧化硅纳米颗粒对于靶向aPDT非常有效，为对抗AMR提供了一种有力的策略。
