The formulation of nanoparticles with intrinsically therapeutic properties in a tailorable and appropriate manner is critical in nanomedicine for effective treatments of infectious diseases. Here, we present a biomedical strategy to formulate silver nanoparticles (AgNPs) as intrinsically therapeutic agents for the treatment of Staphylococcus aureus (S. aureus) keratitis. Specifically, AgNPs are controllably obtained as spheres, wrapped with a biopolymer, and varied in sizes. in vitro and in vivo studies indicate that biological interactions between the AgNPs and corneal keratocytes, S. aureus bacteria, and blood vessels are strongly determined by the particle sizes. As the size increased from 3.3 ± 0.7 to 37.2 ± 5.3 nm, the AgNPs exhibit better ocular biocompatibility and stronger antiangiogenic activity, but poorer bactericidal performance. In a rabbit model of S. Aureus-induced keratitis, intrastromal injection of AgNP formulations (single dose) show substantial influences of particle size on the treatment efficacy. As the trade-off, AgNPs with medium size of 15.0 ± 3.6 nm reveal as the best therapeutic agent that could offer ∼5.6 and ∼9.1-fold greater corneal thickness recovery respectively compared to those with smaller and larger sizes at 3 days post-administration. These findings suggest an important advance in structural design for formulating intrinsically therapeutic nano-agents toward the efficient management of infectious diseases.
Keywords: Infectious keratitis; Nanoscale therapeutics; Silver nanoparticles; Size effects.
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