Yedavally Harita, Gasbarri Matteo, van Dijl Jan Maarten, Stellacci Francesco, Salvati Anna
University of Groningen, Department of Nanomedicine and Drug Targeting, Groningen Research Institute of Pharmacy, Groningen, The Netherlands.
Institute of Materials, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
J Mater Chem B. 2025 Oct 3. doi: 10.1039/d5tb00961h.
Nanomedicine can offer novel strategies in the fight against antimicrobial resistance. Nano-sized drug carriers can be used to deliver antibiotics to their target to treat infections and some nanomaterials themselves have antimicrobial properties. Here, small amphiphilic gold nanoparticles with mixed ligand surfaces have been investigated for their potential use against bacterial infections in different settings. Owing to their unique surface properties, these nanoparticles are known to directly penetrate cell membranes, instead of entering cells by energy-dependent mechanisms of endocytosis, as observed for most nanomaterials. Therefore, we aimed to explore whether this capacity could be exploited to target and eliminate bacteria. To this end, different antibiotic-loaded small amphiphilic gold nanoparticles were prepared and their antimicrobial activity against the human pathogen was demonstrated. Next, we tested whether the antibiotic-loaded nanoparticles could be used to treat intracellular infections, as well as to penetrate and eradicate biofilms. In the case of intracellular infections, nanoparticle uptake was accompanied by a mild decrease in the intracellular bacterial population. In the case of biofilms, instead, the nanoparticles were able to penetrate throughout the thickness of the biofilm, rather than only reaching the upper layers, as observed for most nanomaterials. Moreover, both the amphiphilic gold nanoparticles themselves and the antibiotic-loaded variants strongly induced death of biofilm-embedded bacteria.
纳米医学可为对抗抗菌耐药性提供新策略。纳米尺寸的药物载体可用于将抗生素递送至靶点以治疗感染,并且一些纳米材料本身就具有抗菌特性。在此,对具有混合配体表面的两亲性小金纳米颗粒在不同情况下对抗细菌感染的潜在用途进行了研究。由于其独特的表面性质,已知这些纳米颗粒可直接穿透细胞膜,而不像大多数纳米材料那样通过能量依赖的内吞作用机制进入细胞。因此,我们旨在探索这种能力是否可用于靶向和消除细菌。为此,制备了不同的负载抗生素的两亲性小金纳米颗粒,并证明了它们对人类病原体的抗菌活性。接下来,我们测试了负载抗生素的纳米颗粒是否可用于治疗细胞内感染,以及穿透和根除生物膜。在细胞内感染的情况下,纳米颗粒的摄取伴随着细胞内细菌数量的轻微减少。而在生物膜的情况下,与大多数纳米材料仅能到达生物膜上层不同,这些纳米颗粒能够穿透整个生物膜厚度。此外,两亲性金纳米颗粒本身以及负载抗生素的变体都强烈诱导生物膜包埋细菌的死亡。