College of Health and Life Sciences, Hamad Bin Khalifa University, Doha, Qatar.
College of Science and Engineering, Hamad Bin Khalifa University, Doha, Qatar.
PLoS One. 2020 Apr 10;15(4):e0231276. doi: 10.1371/journal.pone.0231276. eCollection 2020.
Alloyed metallic nanoparticles of silver and copper are effective against intracellular infection. However, systemic toxicity may arise due to the non-specific delivery of the nanoparticles. In addressing the issue, this study deals with the targeting of silver-copper-boron (ACB) nanoparticles to infected osteoblasts, which could decrease systemic toxicity and form the basis of targeting specific markers expressed in bone infections.
ACB nanoparticles were synthesized and conjugated to the Cadherin-11 antibody (OBAb). The effect of targeting nanoparticles against extracellular and intracellular S. aureus was determined by enumeration of bacterial growth. The binding of the targeting nanoparticles to infected osteoblasts as well as the visualization of live/dead bacteria due to treatment was carried out using fluorescence microscopy. MTT assay was used to determine the viability of osteoblasts with different concentrations of the nanoparticles.
The ACB nanoparticles conjugated to OBAb (ACB-OBAb) were effective against extracellular S. aureus. The ACB-OBAb nanoparticles showed a 1.32 log reduction of intracellular S. aureus at a concentration of 1mg/L. The ACB-OBAb nanoparticles were able to bind to the infected osteoblast and showed toxicity to osteoblasts at levels ≥20mg/L. Also, the percentage of silver, copper, and boron in the nanoparticles determined the effectiveness of their antibacterial activity.
The ACB-OBAb nanoparticles were able to target the osteoblasts and demonstrated significant antibacterial activity against intracellular S. aureus. Targeting shows promise as a strategy to target specific markers expressed on infected osteoblasts for efficient nanoparticle delivery, and further animal studies are recommended to test its efficacy in vivo.
银铜合金纳米颗粒对细胞内感染具有有效作用。然而,由于纳米颗粒的非特异性递送,可能会出现全身毒性。为了解决这个问题,本研究致力于将银-铜-硼(ACB)纳米颗粒靶向感染的成骨细胞,这可以降低全身毒性,并为靶向在骨感染中表达的特定标志物提供基础。
合成了 ACB 纳米颗粒并将其与钙黏蛋白 11 抗体(OBAb)缀合。通过计数细菌生长来确定针对细胞外和细胞内金黄色葡萄球菌的靶向纳米颗粒的效果。使用荧光显微镜进行靶向纳米颗粒与感染的成骨细胞的结合以及由于治疗而导致的活/死细菌的可视化。使用 MTT 测定法测定不同浓度的纳米颗粒对成骨细胞活力的影响。
缀合到 OBAb 的 ACB 纳米颗粒(ACB-OBAb)对细胞外金黄色葡萄球菌有效。ACB-OBAb 纳米颗粒在 1mg/L 的浓度下对细胞内金黄色葡萄球菌的减少量为 1.32 对数。ACB-OBAb 纳米颗粒能够与感染的成骨细胞结合,并在≥20mg/L 的水平上对成骨细胞表现出毒性。此外,纳米颗粒中银、铜和硼的百分比决定了其抗菌活性的有效性。
ACB-OBAb 纳米颗粒能够靶向成骨细胞,并对细胞内金黄色葡萄球菌表现出显著的抗菌活性。靶向作为一种策略具有很大的前景,可用于针对感染的成骨细胞表达的特定标志物进行有效的纳米颗粒递药,建议进行进一步的动物研究以测试其在体内的疗效。