Treatment of Multidrug‐Resistant Bacterial Infections Using Quantum Dots

Abstract

Multidrug‐resistant (MDR) bacterial infections remain a major threat to public health, despite strides made in antibiotic development in the past century. The rise of MDR infections has demonstrated the dire need for new treatment strategies against infectious disease. MDR bacteria are predicted to cause ten million deaths annually worldwide by 2050, more than all cancers combined, unless significant strides are made in treatment options. While pharmaceutical companies devote years to develop a single drug for a single ailment, bacteria are quick to adapt, and MDR bacterial strains appear within only a couple years of the release of a new antibiotic. Our antibiotic discovery pipelines must accommodate the necessary shift away from traditional small molecule therapies toward more adaptive drugs.Here, we investigate new ways of combating MDR bacteria and apply those methods in vivo to optimize them for clinical use. We present a novel method for the treatment of infections caused by MDR bacteria: antibiotic photoactivated semiconductor nanoparticles called quantum dots (QDs). Photoactivated QDs kill bacteria by producing superoxide, which targets iron clusters in bacterial cells, and additionally have been shown to potentiate the activity of antibiotics against resistant bacteria. We have previously shown that this specific generation of superoxide allows for killing of bacterial cells without causing toxicity to surrounding mammalian cells in vitro. Indium phosphide (InP) QDs injected subcutaneously into mice caused no measured toxicity, measured through body weight, organ histology, and inflammation and oxidative stress markers in serum, to the host animal after six consecutive days of treatment. InP QDs are activated by near‐infrared (NIR) light, which was provided to the injection site using high‐intensity LEDs. We then used InP QDs to treat subcutaneous abscesses of MDR clinical isolate Escherichia coli in mice. As NIR light has high transmittance through skin and tissue, QDs injected under the skin were sufficiently activated for bacterial killing. We observed decreased bacterial count by QD dosages of 2 and 4 μM compared to PBS treatment. A 6000‐fold drop in abscess bacterial viability was observed in mice treated with 4 μM QDs compared to PBS control.This novel approach to treatment of infectious disease could provide necessary alternatives to small‐molecule drugs. The QDs offer a new method of using superoxide to kill bacteria, including bacteria that have developed resistance to small‐molecule drugs. Our QDs could revolutionize last‐resort treatments of burn and wound infections, with the potential to be expanded to other infection types.