Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next-generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body’s innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

Hydrophobicity has limited the efficiency of many drugs. To improve this, gold–silver alloy nanocomposites covered with carbon-based quantum dots were synthesized as a platform to reduce the drugs’ hydrophobicity. Using the hydrophobic drug Andrographolide as a model, it was demonstrated that these nanocomposites can decrease Andrographolide’s hydrophobicity (Log P from 2.632 to 0.56) without encapsulating the drug. Entry within prostate cancer (PC-3) cells and in vitro localization of the nanocomposites and Andrographolide was observed qualitatively via confocal microscopy and their identity confirmed by SERS inside the PC-3 cells. MTS assays demonstrated the carbon-based quantum dot layer covering the metal core of the nanocomposites stabilizes the oxidation rate of the nanocomposite’s core metals. This was observed by a decrease in cytotoxicity in PC-3 cells when compared to other gold or silver nanosystems for similar timeframes published in the literature.