BACKGROUND In orthopedics, the treatment of implant-associated infections represents a high challenge. Especially, potent antibacterial effects at implant surfaces can only be achieved by the use of high doses of antibiotics, and still often fail. Drug-loaded magnetic nanoparticles are very promising for local selective therapy, enabling lower systemic antibiotic doses and reducing adverse side effects. The idea of the following study was the local accumulation of such nanoparticles by an externally applied magnetic field combined with a magnetizable implant. The examination of the biodistribution of the nanoparticles, their effective accumulation at the implant and possible adverse side effects were the focus. In a BALB/c mouse model (n = 50) ferritic steel 1.4521 and Ti90Al6V4 (control) implants were inserted subcutaneously at the hindlimbs. Afterwards, magnetic nanoporous silica nanoparticles (MNPSNPs), modified with rhodamine B isothiocyanate and polyethylene glycol-silane (PEG), were administered intravenously. Directly/1/7/21/42 day(s) after subsequent application of a magnetic field gradient produced by an electromagnet, the nanoparticle biodistribution was evaluated by smear samples, histology and multiphoton microscopy of organs. Additionally, a pathohistological examination was performed. Accumulation on and around implants was evaluated by droplet samples and histology. RESULTS Clinical and histological examinations showed no MNPSNP-associated changes in mice at all investigated time points. Although PEGylated, MNPSNPs were mainly trapped in lung, liver, and spleen. Over time, they showed two distributional patterns: early significant drops in blood, lung, and kidney and slow decreases in liver and spleen. The accumulation of MNPSNPs on the magnetizable implant and in its area was very low with no significant differences towards the control. CONCLUSION Despite massive nanoparticle capture by the mononuclear phagocyte system, no significant pathomorphological alterations were found in affected organs. This shows good biocompatibility of MNPSNPs after intravenous administration. The organ uptake led to insufficient availability of MNPSNPs in the implant region. For that reason, among others, the nanoparticles did not achieve targeted accumulation in the desired way, manifesting future research need. However, with different conditions and dimensions in humans and further modifications of the nanoparticles, this principle should enable reaching magnetizable implant surfaces at any time in any body region for a therapeutic reason.

中文翻译：

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磁性纳米多孔二氧化硅纳米粒子在骨科中作为药物载体的生物分布，生物相容性和目标积累。

背景技术在骨科中，与植入物相关的感染的治疗代表着高挑战。特别是，在植入物表面的强效抗菌作用只能通过使用高剂量的抗生素来实现，并且仍然经常失败。载有药物的磁性纳米颗粒对于局部选择性治疗非常有前途，可以降低全身性抗生素剂量并减少不良副作用。以下研究的思想是通过外部施加的磁场与可磁化植入物相结合而使此类纳米颗粒局部聚集。研究的重点是纳米颗粒的生物分布，它们在植入物上的有效积累以及可能的不良副作用。在BALB / c小鼠模型（n = 50）中，将铁素体钢1.4521和Ti90Al6V4（对照）植入物皮下插入后肢。之后，静脉内施用经罗丹明B异硫氰酸酯和聚乙二醇-硅烷（PEG）修饰的磁性纳米多孔二氧化硅纳米颗粒（MNPSNP）。在随后施加电磁铁产生的磁场梯度后的第1/7/21/42天，直接通过涂片样本，器官的组织学和多光子显微术评估了纳米颗粒的生物分布。另外，进行了病理组织学检查。通过液滴样品和组织学评估植入物上和周围的积累。结果临床和组织学检查显示，在所有调查时间点，小鼠均未发现与MNPSNP相关的变化。尽管被聚乙二醇化，但MNPSNPs主要被困在肺，肝和脾中。随着时间的流逝，他们表现出两种分布模式：血液，肺，和肾脏，肝脏和脾脏缓慢减少。MNPSNPs在可磁化植入物上及其区域内的积聚非常低，与对照无显着差异。结论尽管单核吞噬细胞系统捕获了大量纳米颗粒，但在受影响的器官中未发现明显的病理形态学改变。这显示了静脉内施用后MNPSNP的良好的生物相容性。器官摄取导致植入区域中MNPSNP的利用率不足。因此，纳米颗粒无法以期望的方式实现目标积累，这表明了未来的研究需求。但是，随着人类的条件和尺寸不同以及纳米粒子的进一步修饰，