Understanding a complex interaction between therapeutic nanoparticles and biological entities is crucially important for the development of effective disease treatments in the modern nanopharmaceuticals and nanomedicines. Herein, we present a strategy to thoroughly assess geometrical impacts of silver nanoparticles (AgNPs, one of the most promising nanotherapeutic agents) on their biological activities toward treatment of Staphylococcus aureus (S. aureus)-induced keratitis. Specifically, three types of differently shaped AgNPs including silver nanorods (R-Ag), silver nanotriangles (T-Ag), and silver nanospheres (SAg) are employed and interferences of particle surface area and functionality are eliminated to reflect purely geometric effects. Ocular biocompatibility studies on rabbit corneal keratocytes reveal that SAg is the least cytotoxic agent while R-Ag, because of its strongest cellular uptake, induces highest cytotoxic levels. Moreover, SAg is demonstrated to outperform R-Ag and T-Ag in killing S. aureus, possibly due to a predominance of specific particle density and high-atom-density {111} facets of the SAg when interacting with the bacteria. In contrast, owing to its predominance of sharp-tip effects on vascular endothelial cells, R-Ag can suppress blood vessel development in cornea at a greatest extent. In a rabbit model of S. aureus-induced keratitis, intrastromal administration of the differently shaped AgNPs exhibits critical roles of the particle geometry at comparable conditions (i.e., total surface area and functionality) in attenuating progression of S. aureus-induced keratitis. As a compromise among ocular biocompatibility, anti-bacterial activity, and anti-angiogenic capability, SAg shows as the most effective agent that could repair infectious corneal tissues 1.2 and 4-fold greater than the anisotropic counterparts (R-Ag and T-Ag). These findings therefore suggest a promising strategy for a clear-cut evaluation on geometric effects of therapeutic nanoparticles toward preclinical treatment of eye-related microbial infections.

理解治疗性纳米颗粒与生物实体之间复杂的相互作用对于开发现代纳米药物和纳米药物中有效的疾病治疗至关重要。在这里，我们提出了一种策略，以彻底评估银纳米颗粒（AgNPs，最有前途的纳米治疗剂之一）对其对金黄色葡萄球菌（S. aureus）诱发的角膜炎的生物活性的几何影响。具体而言，包括银纳米棒（R-Ag），银纳米三角形（T-Ag）和银纳米球（S使用Ag），消除了颗粒表面积和功能的干扰，以反映纯几何效果。对兔角膜角膜细胞的眼生物相容性研究表明，S Ag是最小的细胞毒性剂，而R-Ag由于其最强的细胞摄取能力，诱导出最高的细胞毒性水平。此外，在杀死金黄色葡萄球菌方面，S Ag被证明优于R-Ag和T-Ag ，这可能是由于与细菌相互作用时S Ag具有特定的颗粒密度和高原子密度{111}面。相反，由于R-Ag主要对血管内皮细胞产生尖锐作用，因此它可以最大程度地抑制角膜中的血管发育。在金黄色葡萄球菌的兔子模型中-诱导的角膜炎，不同形状的AgNPs的基质内给药在可比条件下（即，总表面积和功能性）在减缓金黄色葡萄球菌-诱导的角膜炎的进展中显示了颗粒几何形状的关键作用。作为一种在眼生物相容性，抗菌活性和抗血管生成能力之间的折衷方案，S Ag可以作为修复感染性角膜组织的最有效药剂，比各向异性的同种异物（R-Ag和T-Ag）多1.2到4倍。 ）。因此，这些发现提出了一种有前途的策略，可以对治疗性纳米颗粒对临床前治疗与眼部相关的微生物感染的几何效果进行清晰评估。