Efficient photodynamic antibacterial activity relies on the close interfacial association between photosensitizers and bacterial surfaces. While cationic functional groups can enhance bacterial binding, they often cause nonspecific membrane disruption and substantial dark toxicity. Here, we demonstrate that engineering a mixed-charge surface on conjugated oligomer nanoparticles enables programmable interfacial interactions and, consequently, controllable antibacterial performance. Charge-complementary conjugated oligomers, OFTF(+) bearing quaternary ammonium groups, and OFTF(-) bearing carboxyl groups, were assembled into photofunctional nanoparticles (OFTFNPs) by controlling their molar ratio. The mixed-charge surface maintained stable bacterial binding while reducing the overly strong electrostatic contact. This shifted the dominant interaction contribution toward hydrophobic association, thereby reducing nonspecific damage. Based on the balanced nano-bio interface, OFTFNPs predominantly generate reactive oxygen species via a Type II mechanism upon light irradiation, achieving the eradication of bacteria with minimal dark toxicity and improved cytocompatibility relative to OFTF(+) alone. These results demonstrate that mixed-charge surface engineering is a practical approach for separating potent photodynamic antibacterial efficacy from cationic dark cytotoxicity in photosensitizer platforms.
Yang et al. (Fri,) studied this question.