Editors' ChoiceBACTERIAL KERATITIS

Counting on carbon quantum dots to clear infection

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Science Translational Medicine  19 Jul 2017:
Vol. 9, Issue 399, eaao0969
DOI: 10.1126/scitranslmed.aao0969

Abstract

Carbon quantum dots safely treat corneal bacterial infection using their membrane-disrupting positive charge.

The increasing resistance of infections to conventional antibiotics has motivated the development of new therapeutic strategies. Infection of the cornea, known as keratitis, often requires particularly urgent attention. If left untreated, it can quickly progress to cause scarring and even blindness in severe cases. Most infectious keratitis is bacterial and occurs after corneal injury, surgery, or contact lens use. Pseudomonas aeruginosa and Staphylococcus aureus are frequent causes of bacterial keratitis, and nosocomial multidrug resistant infections, including methicillin-resistant S. aureus (MRSA), have been noted in at-risk populations. Although antimicrobial materials, such as silver, have long been used in skin wound dressings, ointments, and implants, delivery and toxicity challenges have made it difficult to apply these antimicrobials to ocular infections.

In a recent report, Jian et al. address these issues using a relatively simple nanoformulation of spermadine, which is an aliphatic polyamine widely found in plants, animals, and microbes. By heating the spermadine to 200 to 300°C and purifying with straightforward centrifugation and dialysis, the authors produced monodisperse nanoparticles 6 nm in diameter. The material is weakly fluorescent and thus classifies as a carbon quantum dot (CQD), which is a carbon-based nanoparticle (<10 nm) with tunable fluorescence properties similar to conventional quantum dots that are based on semiconductor materials. The combination of the CQD shape and highly positive charge makes the material especially disruptive to both gram-negative and gram-positive bacteria. In vitro the CQD inhibited bacterial growth with 2500-fold greater potency than unprocessed spermidine, and also outperformed nanoparticles made of either silver or the antimicrobial polyamine polyethylenimine.

In a rabbit model of bacterial keratitis, topical delivery of the CQD was more effective at killing bacteria than silver nanoparticles. The authors presented data to suggest that CQD delivery is facilitated by the material’s ability to transiently induce the opening of tight junctions in the corneal epithelium. The CQD also performed at least as well as equivalent doses of pharmacy-grade sulfamethoxazole monotherapy, but other common antibiotics such as ciprofloxacin and vancomycin were not tested. Preliminary evaluation of CQD biocompatibility showed negligible toxicity, especially compared with silver nanoparticles; however, higher doses should be tested. Although the spermidine CQD’s fluorescent activity has little relevance to its therapeutic activity, it nevertheless shows potential as a dependable antibiotic to treat ocular bacterial infections.

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