A supramolecular biofilm disruptor based on cationic macrocyclic amphiphiles to eradicate bacterial biofilm-associated infections

Biofilm is closely associated with human bacterial infections, and the inherent resistance of biofilms to antibiotics poses a significant challenge to the antibiotic treatments. Thus, developing safe and efficient anti-biofilm agents are urgently needed. Here, we report a supramolecular biofilm disruptor, choline-functionalized calix[4]arene amphiphiles (ChC4A), for eradicating bacterial biofilm-associated infections. Benefited from favorable amphiphilic nature and molecular recognition ability, the ChC4A can self-assemble into nanoparticles with remarkably low critical aggregation concentration and quantitatively package antibiotics through host–guest interaction. More importantly, the resultant supramolecular nanoformulation effectively eliminate the intractable mature biofilms by the synergistic effect of enhanced penetration and disruption for biofilm barriers and the controlled release of antibiotics at biofilm microenvironment. Furthermore, in vivo studies demonstrated that treatment with this macrocyclic-antibiotic complex amphiphiles can efficiently eradicate bacterial infections without unwanted side effect on normal tissues. This work represents a promising supramolecular strategy for combating bacterial biofilm-associated infections and provides new perspectives for the development of advanced anti-biofilm therapies.