Characterization of Nano-decorated L. Lactis as a putative Theranostic Agent

Abstract Background. Lactococcus lactis has a long history of safe food and pharmaceutical applications. Its non-pathogenic nature and presence in the human microbiome also make it a promising candidate for theranostic applications. Nanoparticle coating offers a means to equip bacteria with spatial-temporal manipulation capability, cargo release control, and life cycle modulation by exogenous signals such as ultrasounds. Surprisingly, scientific literature lacks any reference data concerning L. lactis-based platforms. Methods. Lipid-shelled, iron-doped zinc nanoparticles (ZnO-NPs) were generated. Bacteria and nanoparticle cultures with and without ultrasound stimulation were studied by confocal fluorescence microscopy and optical densitometry viability assays. Results. Bacterial growth curve was unaffected by nanoparticles concentrations up to 100 µg/ml at 48 hours, nor by applying ultrasound energies of 1 MHz frequency, 0.9 W/cm² acoustic density and 2-minute exposure. Conclusions. Lipid-shelled ZnO-NPs are well tolerated by L. lactis and can be co-localized with bacteria in due time. L. lactis resist to ultrasound stimulations, even when in presence with NPs with energies sufficient to reach deep tissues in humans that would result in eukaryotic cell apoptosis. Our findings provide strong support for the validity of this approach in a variety of fields and set useful protocols for researchers. We discuss limitations and future research towards theranostic applications.