Nanorobots to fight bacterial infections

Researchers develop self-contained micro- and nanorobots with antimicrobial activity, capable of attacking bacteria in the site of infection. The work has been led by Samuel Sánchez (Institute for Bioengineering of Catalunya (IBEC) and Cesar de la Fuente-Núñez (University of Pennsylvania, USA). The new technology, tested in mice, is a valuable tool for the treatment of bacterial infections in a controlled and localized way. In a future not so far, it could help combat infections.

One death every 3 seconds in 2050, or, in other words, approximately 10 million deaths. This is the estimate of the impact that resistance to antibiotics will have in a few years, bearing in mind that they are now the 4th cause of death in hospitals in the USA. This complex health situation is largely due to the wide and insecure range of action of current antibiotics and the lack of efficient administration methods that release antibiotics only in the place of infection and not in a systemic way, resulting in the emergence of resistant bacteria.

With the aim of providing solutions to this problem, a group of international researchers led by research professor ICREA Samuel Sánchez of the Institute for Bioengineering of Catalonia (IBEC) and leader of the group “Smart Nano-Bio Devices“, and by César de la Fuente-Núñez (University of Pennsylvania, USA), have developed micro- and nanorobots that are capable of autonomously carrying peptides (small proteins) bactericides to the site of infection. The work has recently been published in the prestigious journal ACS Nano.

Autonomous movement and transport of antimicrobial peptides

Micro- and nanomotors developed in this work are based on porous silica and are driven autonomously by a chemical reaction, the catalysis of the enzyme urease, which uses urea as biocompatible fuel. These tiny robots have been coated with antimicrobial peptides that have strong antibiotic action. One of them is a peptide of natural origin and the other is a synthetic peptide derived from wasp venom. Both perform their bactericide function by destabilising the cell membrane of bacteria, their protective envelope. The bactericidal activity of these engines has been tested on the micro and nanoscales (one thousand and one million times smaller than one millimetre, respectively) and in five clinically relevant bacteria species. In all cases they proved to be effective.

Our nanorobots combine navigation, catalysis and bactericide capacity to carry antimicrobial charges to specific sites of infection. Xavier Arqué, first co-author of the work (IBEC)

Activity demonstrated in mice

To test micro- and nanorobots under in vivo conditions, researchers treated mice that had an infected wound with Acinetobacter baumannii, a bacterium resistant to most antibiotics and which may cause severe pneumonia and urinary tract infections. Micro- and nanorobots loaded with antimicrobial peptides were inoculated at one end of the wound and the area was treated with urea, the fuel needed for self-propulsion.

Four days after treatment with the nanorobots, we analysed the amount of bacteria in the wound and we found out that it had been reduced 3 times. Marcelo Torres, first co-author of the work (University of Pennsylvania)

The key of the successful treatment has been the displacement of micro- and nanorobots throughout the area of the wound (1 cm2), which has allowed antimicrobial peptides to be dispersed to a much larger surface. On the contrary, wounds treated with free antimicrobial peptides showed a reduction in the number of bacteria only in the inoculation zone.

This new bioengineering tool opens the doors to the use of bioactive and autonomous nanorobots in the clinic for the treatment of infectious diseases.

Reference article: Xavier Arqué, Marcelo D. T. Torres, Tania Patiño, Andreia Boaro, Samuel Sánchez, Cesar de la Fuente-Nunez. Autonomous Treatment of Bacterial Infections in Vivo Using Antimicrobial Micro- and Nanomotors. April 29, 2022. DOI: 10.1021/acsnano.1c11013