Biofilm infections are a global public health threat, necessitating new treatment strategies. Biofilm formation also contributes to the development and spread of multidrug-resistant (MDR) bacterial strains. Biofilm-associated chronic infections typically involve colonization by more than one bacterial species. The co-existence of multiple species of bacteria in biofilms exacerbates therapeutic challenges and can render traditional antibiotics ineffective. Polymeric nanoparticles offer alternative antimicrobial approaches to antibiotics, owing to their tunable physico-chemical properties. Here, we report the efficacy of poly(oxanorborneneimide) (PONI)-based antimicrobial polymeric nanoparticles (PNPs) against multi-species bacterial biofilms. PNPs showed good dual-species biofilm penetration profiles as confirmed by confocal laser scanning microscopy. Broad-spectrum antimicrobial activity was observed, with reduction in both bacterial viability and overall biofilm mass. Further, PNPs displayed minimal fibroblast toxicity and high antimicrobial activity in an in vitro co-culture model comprising fibroblast cells and dual-species biofilms of Escherichia coli and Pseudomonas aeruginosa. This study highlights a potential clinical application of the presented polymeric platform.

Bioorthogonal chemistry introduces nonbiogenic reactions that can be performed in biological systems, allowing for the localized release of therapeutic agents. Bioorthogonal catalysts can amplify uncaging reactions for the in situ generation of therapeutics. Embedding these catalysts into a polymeric nanoscaffold can protect and modulate the catalytic activity, improving the performance of the resulting bioorthogonal “polyzymes”. Catalysts based on nontoxic metals such as gold(I) are particularly attractive for therapeutic applications. Herein, we optimized the structural components of a metal catalyst to develop an efficient gold(I)-based polyzyme. Tailoring the ligand structure of gold phosphine-based complexes, we improved the affinity between the metal complex and polymer scaffold, resulting in enhanced encapsulation efficiency and catalytic rate of the polyzyme. Our findings show the dependence of the overall polyzyme properties on the structural properties of the encapsulated metal complex.

Fungal infections represent a significant global health challenge. Candida albicans is a particularly widespread pathogen, with both molecular and biofilm-based mechanisms making it resistant to or tolerant of available antifungal drugs. This study reports a combination therapy, active against C. albicans, utilizing terbinafine and essential oils incorporated into a gelatin-based nanoemulsion system (T-GNE). Eugenol and methyl eugenol/terbinafine T-GNEs had an additive efficacy, while carvacrol (CT-GNE) worked synergistically with terbinafine, providing effective antifungal treatment with minimal mammalian cell toxicity. Confocal microscopy demonstrated that CT-GNE penetrated the dense C. albicans biofilm and disrupted the fungal cell membrane. Overall, the combination of essential oils with terbinafine in GNE provided a promising treatment for fungal biofilms.