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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> The resulting positively charged particles effectively associated with Gram-positive <i>Staphylococcus aureus</i>, forming co-aggregates with bacterial cells and exhibiting antibacterial activity tenfold greater than free copper nanoparticles. In co-cultures of <i>S. aureus</i> and the amylase-producing bystander species, <i>Bacillus subtilis</i>, enzymatic degradation of the copper-starch nanoparticles increased antibacterial activity against <i>S. aureus</i> by 44%. <b>Conclusions:</b> 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.