Open Access Kent State (OAKS)

Antibiotic resistant bacteria strains have come into focus in recent years; these bacteria are unable to be treated by normal antibiotics and have resulted in an increase in the number of mortalities by infectious diseases for the first time in decades. The antibiotic properties of gallium have been studied in recent years. Bacterial cells require iron to function; gallium, which has very similar ionic size and charge, travels through the body by the same mechanisms (i. e. siderophores) and is delivered to the cell by the same uptake pathways. Gallium attacks the cell by a “Trojan horse” method: it takes the place of iron in the metabolic pathway of the cell, but since it does not possess iron’s redox properties, gallium cannot do iron’s job, and the cell is forced to undergo apoptosis (programmed self-death). Gallium has also been shown to penetrate biofilms, self-produced matrices created by bacteria to protect themselves. Gallium was utilized in therapy as Ganite®, a gallium nitrate solution; however, 12.5% of patients had renal failure because gallium precipitated as gallium hydroxide and prevented proper kidney function. Our plan is to utilize gallium cysteinate nanoparticles to kill antibiotic-resistant strains of bacteria such as Staphylococcus aureus and Pseudomonas aeruginosa that will not cause aggregation and kidney death. In addition, properties of a copper-bound gallium cysteinate nanoparticle in these therapies will be explored.

The number of antibiotic-resistant bacterial strains has been dramatically increased over the past few decades[1]. With bacteria constantly evolving, humans are unable to discover new antibiotics fast enough to keep an upper hand in this race[2]. It is therefore vital to explore novel non-antibiotic-based antimicrobial drugs with high efficacy and different mechanisms of action to inhibit bacterial growth. This study was focused on designing a biocompatible and efficient nanocomposite drug delivery system containing Vitamin C-Copper nanoparticles (CuNPs) incorporated into alumina hydrogels. It has been demonstrated that γ-alumina hydrogels with CuNPs embedded in the hydrogel network can be readily formed by hydrolysis reactions of aluminum isopropoxide in water, followed by incorporation of CuNPs. The products obtained in both nanoparticles and composite forms were fully characterized by dynamic light scattering (DLS), X-ray powder diffraction (XRD), scanning electron microscopy (SEM) and Transmission electron microscopy (TEM). The CuNPs released from the hydrogels are expected to exhibit improved cellular penetration via endocytosis and could trigger apoptosis by generating Reactive oxygen species (ROS) in bacterial cells. The antibacterial efficacy of CuNPs was examined and found to be highly active against Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA) as well as methicillin-resistant Staphylococcus aureus (MRSA) and Multi drug-resistant Pseudomonas aeruginosa (MDRPA).

References:

1. Kaushik, Neha, Nizam Uddin, Geon Bo Sim, Young June Hong, Ku Youn Baik, Chung Hyeok Kim, Su Jae Lee, Nagendra Kumar Kaushik, and Eun Ha Choi. "Responses of solid tumor cells in DMEM to reactive oxygen species generated by non-thermal plasma and chemically induced ROS systems." Scientific reports 5 (2015): 8587.
2. Usman, M. S., El Zowalaty, M. E., Shameli, K., Zainuddin, N., Salama, M., & Ibrahim, N. A. (2013). Synthesis, characterization, and antimicrobial properties of copper nanoparticles. International journal of nanomedicine, 8, 4467.