Target: Drug resistant bacteria

Bacteria have become increasingly resistant to existing drugs, but researchers have developed a nanoparticle designed to evade the immune system and home in on infection sites, and then unleash a focused antibiotic attack.

The researchers are from the Massachusetts Institute of Technology, Bringham and the Women’s Hospital. Aleks Radovic-Moreno, and MIT graduate student and lead author of the paper, said that their approach would mitigate the side effects of some antibiotics and protect the beneficial bacteria that normally live inside our body.

First, the team created the new nanoparticles from a polymer capped with polythelyne glycol (PEG), which is commonly used for drug delivery because it is nontoxic and can help nanoparticles travel through the bloodstream by evading detection by the immune system.

Second, they induced the particles to specifically target bacteria. Researchers have previously tried to target particles to bacteria by giving them a positive charge, which attracts them to bacteria’s negatively charged cell walls. However, the immune system tends to clear positively charged nanoparticles from the body before they can encounter bacteria.

To overcome this, the researchers designed antibiotic-carrying nanoparticles that can switch their charge depending on their environment. While they circulate in the bloodstream, the particles have a slight negative charge. However, when they encounter an infection site, the articles gain positive charge, allowing them to tightly bind to bacteria and release their drug payload.

This switch is provoked by the slightly acidic environment surrounding bacteria. Infection sites can be slightly more acidic than normal body tissue if disease-causing bacteria are reproducing rapidly, depleting oxygen. Lack of oxygen triggers a change in bacterial metabolism, leading them to produce organic acids. The body’s immune cells also contribute: Cells called neutrophils produce acids as they try to consume the bacteria.

Once the nanoparticles bind to bacteria, they begin releasing their drug payload, which is embedded in the core of the particle. In their study, the researchers designed the particles to deliver vancomycin used to treat drug resistant infections, but the particle could be modified to deliver other antibiotics or combinations of drugs.

Although further development is needed, the researchers hope the high doses delivered by their particles could eventually help overcome bacterial resistance. “When bacteria are drug resistant, it doesn’t mean they stop responding, it means they respond but only at higher concentrations. And the reason you can’t achieve these clinically is because antibiotics are sometimes toxic, or they don’t stay at that site of infections long enough,” Randovic-Moreno says.

[ Via MIT news]

Photo courtesy: Alec Radovic-Moreno