Abstract
Although conventional antibiotics have evolved as a staple of modern medicine, increasing antibiotic resistance and the lack of antibiotic efficacy against new bacterial threats is becoming a major medical threat. In this work, we employ single-walled carbon nanotubes (SWCNTs) known to deliver and track therapeutics in mammalian cells via intrinsic near-infrared fluorescence as carriers enhancing antibacterial delivery of doxycycline and methicillin. SWCNTs dispersed in water by antibiotics without the use of toxic bile salt surfactants facilitate efficacy enhancement for both antibiotics against Staphylococcus epidermidis strain showing minimal sensitivity to methicillin. Doxycycline to which the strain did not show resistance in complex with SWCNTs provides only minor increase in efficacy, whereas the SWCNTs/methicillin complex yields up to 40-fold efficacy enhancement over antibiotics alone, suggesting that SWCNT-assisted delivery may circumvent antibiotic resistance in that bacterial strain. At the same time SWCNT/antibiotic formulations appear to be less toxic to mammalian cells than antibiotics alone suggesting that nanomaterial platforms may not restrict potential biomedical applications. The improvement in antibacterial performance with SWCNT delivery is tested via 3 independent assays—colony count, MIC (Minimal Inhibitory Concentration) turbidity and disk diffusion, with the statistical significance of the latter verified by ANOVA and Dunnett’s method. The potential mechanism of action is attributed to SWCNT interactions with bacterial cell wall and adherence to the membrane, as substantial association of SWCNT with bacteria is observed—the near-infrared fluorescence microscopy of treated bacteria shows localization of SWCNT fluorescence in bacterial clusters, scanning electron microscopy verifies SWCNT association with bacterial surface, whereas transmission electron microscopy shows individual SWCNT penetration into bacterial cell wall. This work characterizes SWCNTs as novel advantageous antibiotic delivery/imaging agents having the potential to address antibiotic resistance.
Highlights
Due to the misuse and overuse of conventional antibiotics, resistant infections are on the rise [1]
Microbial growth inhibition by carbon nanotubes platform was shown before [20], in this work we propose novel non-covalent formulation of existing antibiotics with single-walled carbon nanotubes (SWCNTs) for delivery, imaging, and enhanced antibiotic efficacy
The coating of antibiotics on SWCNTs has been further assessed by Transmission Electron Microscopy (TEM) showing substantial surface coverage (Figure S2)
Summary
Due to the misuse and overuse of conventional antibiotics, resistant infections are on the rise [1] Those include well-known bacterial strains such as Staphylococcus aureus (MRSA) [2], Streptococcus pneumoniae [3] and Mycobacterium tuberculosis [4]. 10 million people will die from resistant infections by the year 2050 [5], not considering the emergence of new resistant strains This mortality prediction exceeds that of cancer and diabetes combined. In response to this crisis, new antibiotics are being developed [6,7]; offering only a temporary solution and, rather, giving rise to multi-drug resistant infections [8]. With mutated bacterial infections being the foundation for many large-scale health issues including M. tuberculosis, MRSA and VRE (Vancomycin-resistant Enterococci) [9,10], the crisis of antibiotic resistance, as well as the need in enhancing antibiotic efficacy becomes a global issue
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