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Over the past several decades, bacteria have become increasingly resistant to available drugs. One strategy that might combat such resistance would be to overwhelm bacterial defenses by using highly targeted nanoparticles to deliver large doses of existing antibiotics.

In a step toward that goal, researchers at the Institute and Brigham and Women’s Hospital have developed a nanoparticle designed to evade the immune system and home in on infection sites to unleash a focused antibiotic attack.

This approach would mitigate the side effects of some antibiotics and protect the beneficial bacteria that normally live inside our bodies, says Aleks Radovic-Moreno, an MIT graduate student and lead author of a recent paper describing the particles in the journal ACS Nano.

The team, led by Institute Professor Robert Langer of MIT and Omid Farokzhad, director of the Laboratory of Nanomedicine and Biomaterials at Brigham and Women’s, created the new nanoparticles from a polymer capped with polyethylene glycol (PEG). PEG is commonly used for drug delivery because it is nontoxic and can help nanoparticles evade detection by the immune system to travel through the bloodstream. 

Their next step was to induce the particles to target bacteria. Researchers have previously tried giving drug-containing particles 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 obstacle, the MIT and Brigham and Women’s team designed nanoparticles that can switch their charge depending on their environment. While they circulate in the bloodstream, the particles have a slight negative charge. But when they encounter an infection site, which tends to be slightly acidic, they gain a positive charge, allowing them to bind tightly to bacteria and release their drug payload. 

These particles were designed to deliver vancomycin, a common treatment for drug-resistant infections, but they 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,” Radovic-Moreno says. “It means they respond, but only at higher concentrations. And the reason you can’t achieve these concentrations clinically is because antibiotics are sometimes toxic, or they don’t stay at that site of infection long enough.” 

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Credit: Aleks Radovic-Moreno

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