Recent advances and future challenges in the use of nanoparticles for the dispersal of infectious biofilms

Increasing occurrence of intrinsically antimicrobial-resistant, human pathogens and the protective biofilm-mode in which they grow, dictates a need for the alternative control of infectious biofilms. Biofilm bacteria utilize dispersal mechanisms to detach parts of a biofilm as part of the biofilm life-cycle during times of nutrient scarcity or overpopulation. We here identify recent advances and future challenges in the development of dispersants as a new infection-control strategy. Deoxyribonuclease (DNase) and other extracellular enzymes can disrupt the extracellular matrix of a biofilm to cause dispersal. Also, a variety of small molecules, reactive oxygen species, nitric oxide releasing compounds, peptides and molecules regulating signaling pathways in biofilms have been described as dispersants. On their own, dispersants do not inhibit bacterial growth or kill bacterial pathogens. Both natural, as well as artificial dispersants, are unstable and hydrophobic which necessitate their encapsulation in smart nanocarriers, like pH-responsive micelles, liposomes or hydrogels. Depending on their composition, nanoparticles can also possess intrinsic dispersant properties. Bacteria dispersed from an infectious biofilm end up in the blood circulation where they are cleared by host immune cells. However, this sudden increase in bacterial concentration can also cause sepsis. Simultaneous antibiotic loading of nanoparticles with dispersant properties or combined administration of dispersants and antibiotics can counter this threat. Importantly, biofilm remaining after dispersant administration appears more susceptible to existing antibiotics. Being part of the natural biofilm life-cycle, no signs of "dispersant-resistance" have been observed. Dispersants are therewith promising for the control of infectious biofilms.