Selective Entropy Gain-Driven Adsorption of Nanospheres onto Spherical Bacteria Endows Photodynamic Treatment with Narrow-Spectrum Activity

Narrow-spectrum antimicrobials specifically eradicate the target pathogens but suffer from significantly lagging development. Photodynamic therapy eliminates cells with reactive oxygen species (ROS) generated upon light irradiation but is intrinsically a wide-spectrum modality. We herein converted photodynamic therapy into a narrow-spectrum modality by taking advantage of a previously unnoticed physics recognition pathway. We found that negatively charged nanospheres undergo selective entropy gain-driven adsorption onto spherical bacteria, but not onto rod-like bacteria. This bacterial morphology-targeting selectivity, combined with the extremely limited effective radii of action of ROS, enabled photodynamic nanospheres to kill >99% of inoculated spherical bacteria upon light irradiation and <1% of rod-like bacteria under comparable conditions, indicative of narrow-spectrum activity against spherical bacteria. This work unveils the bacterial morphology selectivity in the adsorption of negatively charged nanospheres and suggests a new approach for treating infections characterized by overthriving spherical bacteria in niches naturally dominated by rod-like bacteria.