Cancer is amongst the leading causes of death worldwide and patients are more prone to bacterial infections due to their weakened immunity, low numbers of neutrophils, and the alarming emergence of antibiotic resistance in bacteria.
Now, an all women team at the Indian Institute of Technology Delhi (IITD) have proposed a ‘golden’ solution to improve the efficacy of conventional antibiotics. In a recently published article in Nature’s Scientific Reports, the team led by Prof. Shalini Gupta and Prof. Neetu Singh have shown that when an antibiotic is coupled with gold nanoparticles, it enhances the antibiotics’ efficacy by almost 40 percent.
“Present strategies for treating bacterial infections in cancer patients have many drawbacks. Hence, it was important to develop newer ways of dealing with them”, says Prof. Gupta at the Department of Chemical Engineering at IITD.
Prof. Gupta’s team found that coupling the antibiotic sushi3 peptide with gold nanoparticles helped to target the drug directly at the bacteria residing inside cancer cells, making it more effective. According to Dr. Gupta, there are several other benefits of using nanoparticles as a drug delivery vehicle. In addition to being inert and non-toxic to mammalian cells, gold nanoparticles are stable for a longer time, which improves their availability at the site of infection and eventually the efficacy of the antimicrobial drug.
Furthermore, because of their small size and high surface area, it is possible to attach multiple drugs to a single nanoparticle. This increases the concentration of drugs at the target site causing bacteria to die early. “It could be a key step in mitigating the growing menace of antibiotic resistance”, believes Prof. Gupta. Her team tested the antibiotic-coupled nanoparticles on Salmonella typhi and Escherichia coli. The former are known to infect gall bladder cancer cells and the latter reside in the human gut but are opportunistic pathogens, causing infections when the immunity becomes low, like in individuals being treated for cancer.
The gold nanoparticles used in this study were small spheres, around 12 to 20 nanometers wide. They were non-toxic, inert, and could be attached to the antibiotic by a simple, single step chemical process.
Sushi3 peptide is a potent antibiotic, which was first reported in 2003 by a group of Singaporean scientists. It binds to lipopolysaccharides (LPS), a pathogenic component present in cell wall of certain bacteria, leading to rupture or disintegration the cell membrane and ultimately bacterial cell death. The antibiotic peptide kills bacteria this without releasing LPS into the human blood stream, which is beneficial in cases like sepsis where LPS in bloodstream can complicate the clinical condition.
“Coupling antibiotic to gold nanoparticles killed more numbers of bacteria than the antibiotic alone”, said Dr. Gupta talking about the results of the study. Cultured human cells treated with different doses of the antibiotic-nanoparticle conjugate survived, which implied that the conjugate was non-toxic and safe for mammalian cells.
“Bacterial infections and cancer are both undesirable conditions in humans. So, we are designing systems where we couple both the antibiotic and the anti-cancer drug together onto the modified nanoparticles”, remarks Prof. Neetu Singh. “The preliminary results are quite exciting. If the experiments continue to succeed, we will test the nanoparticle-drug conjugates in animal models”, she adds.
So, is there more hope for those battered by cancer and infections? “In future, nanoparticles will make the existing antibiotics more effective and help target cancer cells with lower doses and in lesser time”, signs off Prof. Singh.