Nanomaterials for Fighting Multidrug-Resistant Biofilm Infections

Abstract

Multidrug-resistant bacterial infections represent a dire threat to global health. The development of antibiotic resistance in bacteria coupled with the lack of development of new antibiotics is creating infections requiring antibiotics of last resort, and even some infections for which we have no available treatment. Biofilm-based infections present some of the most challenging targets for treatment. The biofilm matrix provides a physical barrier that can impede access of antibiotics and antimicrobials to resident bacteria. The phenotypic diversity found in biofilms further exacerbates the difficulty of eliminating infections, with quiescent “persister” cells evading therapeutics and re-initiating infections after treatment. Nanomaterials provide a tool for combatting these refractory biofilm infections. The distinctive size regime and physical properties of nanomaterials provide them with the capability to penetrate and disrupt biofilms. Nanomaterials can also access antimicrobial pathways inaccessible to conventional antimicrobials, providing a synergistic strategy for treating biofilm infections. This review will summarize key challenges presented by antibiotic resistance and biofilms when treating infection and provide selected examples of how nanomaterials are being used to address these challenges.

Polymeric Nanoparticles for Drug Delivery

“…Nanoparticle transport has been shown to occur either through the biofilm or through these water-filled pores, but is strongly dependent on charge, with cationic materials favored due to the anionic nature of the biofilm. 42 It is critical that strategies to treat biofilms target persister cells, as to leave some bacteria alive results in the continued spread of infection as well as antimicrobial resistance (the generation of bacteria that are resistant to antimicrobial treatment). Biofilms also develop a gradient in pH, oxygen, and nutrient concentration as a result of the metabolic activity of the microorganisms contained within the film.…”

“…The biofilm also contains water-filled pores that allow for the transport of nutrients into the film. Nanoparticle transport has been shown to occur either through the biofilm or through these water-filled pores, but is strongly dependent on charge, with cationic materials favored due to the anionic nature of the biofilm . It is critical that strategies to treat biofilms target persister cells, as to leave some bacteria alive results in the continued spread of infection as well as antimicrobial resistance (the generation of bacteria that are resistant to antimicrobial treatment).…”

Design of Ultrasound-Driven Charge Interference Therapy for Wound Infection

“…The production and deposition of an exopolysaccharide matrix on wounds can prevent the penetration of antibiotics. Due to their vast and heterogeneous structure, biofilms can protect encased bacteria from the host immune response, such as phagocytosis and the activation of the complement system. − In recent decades, the prevalence of skin infections caused by both Gram-negative and Gram-positive bacteria has surged, leading to hospitalization, bacteremia, and fatalities . Therefore, there is an urgent need to develop effective strategies and therapeutic alternatives capable of treating bacterial infections without relying on conventional antibiotics, while also possessing the ability to penetrate biofilms.…”