Fluorescent silicon nanoparticles-based nanotheranostic agents for rapid diagnosis and treatment of bacteria-induced ker
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ratory of Nanoscale Biochemical Analysis, Institute of Functional Nano and Soft Materials (FUNSOM), and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215123, China 2 Department of Ophthalmology, Children’s Hospital of Soochow University, Soochow University, Suzhou 215123, China § Lu Zhang and Xiaoyuan Ji contributed equally to this work. © Tsinghua University Press and Springer-Verlag GmbH Germany, part of Springer Nature 2020 Received: 17 June 2020 / Revised: 4 August 2020 / Accepted: 4 August 2020
ABSTRACT Recommended as a medical emergency, infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness. Herein, we present a kind of theranostic agents, which are made of vancomycin (Van)modified fluorescent silicon nanoparticles (SiNPs-Van), enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner. Typically, the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro (5 min) and in vivo (10 min), making them an efficacious diagnostic agent for the detection of bacterial keratitis. In addition, the SiNPs-Van feature distinct antimicrobial activity, with superior activity of 92.5% at a concentration of 0.5 μg/mL against Staphylococcus aureus (S. aureus); comparatively, the antimicrobial rate of free vancomycin is 23.3% at the same concentration. We further explore the SiNPs-Van agents as eye drops for therapy of S. aureus-induced bacterial keratitis on rat model. Represented by slit-lamp scores, the keratitis severity of SiNPs-Van-treated corneas is 3.4, which is 59.6% and 77.3% slighter than vancomycin- (8.2 score) and PBS-treated corneas (15.0 score), respectively. The infected corneas recover to normal (1 score) after 7-d of SiNPs-Van treatment. Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents, especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis.
KEYWORDS bacterial keratitis, bio-imaging, theranostic probe, silicon nanoparticles
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Introduction
Infectious keratitis that would lead to corneal opacities is one globally major cause of vision impairment and blindness [1]. Whereas the pathogens have been proved to include bacteria, fungi, viruses and protozoa, proper diagnosis (i.e., infections are definitively confirmed and causative organisms are identified) is critical to initiate aggressive treatments [2]. The prevailing diagnostic techniques are currently Gram stain and culture, typically time-consuming, hours to days, and tedious in manipulation [1, 3]. Nevertheless, infectious keratitis recommended as a medical emergency usually implies an acute and rapid disease progression (e.g., Staphylococcus aureus (S. aureus)-induced keratitis can even cause the loss of vision within days as the complete destruction of corneal stroma is induced), and hence time is absent in this sight-threating disease [4–
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