Targeting of Bacteria Using Amylase-Degradable, Copper-Loaded Starch Nanoparticles

Background/Objectives: The treatment of bacterial infections is complicated by emerging antibiotic resistance. This paper identifies a novel approach with a nanoparticle that targets bacterial surface charge and is responsive to the nutrient environment (i.e., glucose) and presence of metabolically active bystander species (i.e., amylase secretion) within microbial communities. Methods: Thus, metabolically responsive composite nanoparticles (440 ± 58 nm) were fabricated via electrohydrodynamic jetting of a cationic starch polymer incorporating 5–7 nm copper nanoparticles (0.3 wt%). Starch was selected as the base polymer, as it is a common carbon source for amylase-producing bacterial communities, in particular under glucose-limited growth conditions. Results: The resulting positively charged particles effectively associated with Gram-positive Staphylococcus aureus, forming co-aggregates with bacterial cells and exhibiting antibacterial activity tenfold greater than free copper nanoparticles. In co-cultures of S. aureus and the amylase-producing bystander species, Bacillus subtilis, enzymatic degradation of the copper–starch nanoparticles increased antibacterial activity against S. aureus by 44%. Conclusions: This work highlights the potential for metabolically regulated particles as a novel paradigm for selective, narrow-spectrum antibacterial therapies that exploit ecological interactions within microbial communities.