Drug resistance of bacteria has risen to turn into a severe problem globally. It is being exacerbated due to the abusive usage and stagnant development of antibiotics. To overcome the drug resistance in bacteria, combination therapies of multiple antibiotics into one treatment is a common strategy, this methodology, however, is generally quite toxic in vivo, and fails to resolve the aqueous solubility of antibiotics that negatively influences the efficacy of antibiotics. To conquer these existing issues and the drug resistance of bacteria, here I will present our suprmacromolecular strategy which we employ two synthetic non-toxic supramolecular subunits that are able to selectively bind silver ions (Ag+) and small-molecule broad-spectrum antibiotics, respectively, and a third subunit that is capable of selectively targeting bacterial surfaces electrostatically and destabilize their membranes. For these two supramolecular subunits, the related compounds were synthesized and showed strong non-covalent bindings towards Ag+ and antibiotics, respectively, with high binding constants of ~105 and ~103 M-1, respectively. The binding affinity and solubility of these two subunits were modulated by chemically addressing the functional groups of supramolecules. Homopolymers and block copolymers of these functional subunits were then synthesized and further characterized with their chemophysical and biochemical properties (i.e., release kinetics and cycotoxicity). In the presence of the third subunit and after chemical treatment, the corresponding tri-block copolymer yielded polymeric nanomaterial in mixture of organic solvent and water, whose morphology allowed Ag+ and antibiotics stored in the core of nanomaterial to be released sustainably and synergistically. The copolymeric nanomaterial’s efficacy towards both drug resistant Gram-positive/negative bacteria was assessed. The experiments with bacteria show promising results in that this supramacromolecular platform is able to sustainably and synergistically release the Ag+ and antibiotics, killing or inhibiting the growth of the bacteria efficiently.

Overcoming antibiotic resistance via supramacromolecular strategy

256th National Meeting (2018)

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