Development of novel colloidal particles through nanoimprinting technology towards nanoantibiotics

Abstract

A novel class of physical anti-bacterial and potentially anti-viral agents has been proposed based on the shape and size recognition and specific binding to inorganic imprints produced by templating the chosen target pathogens with suitable inorganic material. The products of the templating process are partially fragmented nanoshells which are intended to selectively bind to their biological counterparts, therefore impairing microbial cell growth, replication and infection. Further combinations of the size- and shape-recognising particles with other toxins or conventional antibacterial agents could result in the delivery of high concentration of these agents onto the target cell surface. We have named this class of particles, which are capable of selectively recognising bacterial shape and size, “nanoantibiotics”, due to the architecture of the nano-shells formed around the templated pathogen. The selective binding is driven by the increased area of contact upon recognition of the shape and size between the partial negative replicas of the pathogens and their templates. In this thesis we have tested this concept theoretically by calculating and assessing the DLVO interactions between the nanoantibiotic particles and spherical target cells, analysing the interaction energy between matching and mismatching nanoantibiotic-target particle pairs. The results of these calculations suggest that the binding energy can be orders of magnitude stronger in case of recognition.We have also explored routes of fabrication of the nanoantibiotic particles using gold, zinc, and silica as shell forming materials. Additionally, we conducted a number of experiments which probed their shape and size selectivity using bacterial (Bacillus subtilis) and yeast (Saccharomyces cerevisiae) cells as test microorganisms as well as commercially available latex microspheres which have the advantage of fixed shape with variability in size. Latex particles were used only as a tool to study of the effect of the target particle size on the recognition events. Our experiments showed high levels of nanoantibiotic recognition selectivity which reinforced the concept of these novel antipathogenic agents.Finally, we also developed gold nanoparticle-silica composite nanoantibiotic particles which showed the capability of selective killing of the target microbe when triggered by laser. We demonstrated this by selectively killing yeast in a mixture with other bacterial cells by triggered localised heating on the surface of the yeast cells through laser-induced photothermal effect. Nanoantibiotic particles could be designed to bind and potentially deactivate strains of antibiotic resistant bacteria like MRSA, E .coli and many others where most conventional antibiotics are powerless. Nanoantibiotic particles can also find applications as non-toxic antibacterial agents, for example to prevent harmful bacterial strains of E. coli from growing on food and personal care formulations. They could be of great benefit to the pharmaceutical industry, and in applications in food and personal care sectors by acting as inorganic, long lasting and specific biocides

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