Toward understanding the purely geometric effects of silver nanoparticles on potential application as ocular therapeutics via treatment of bacterial keratitis

Abstract

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.