Light-Activated Antibacterial and Antibiofilm Properties of Photosensitizer-Loaded Polymer-Based Nanocarriers: Role of Hydrophilic–Hydrophobic Balance

The rapid rise of multidrug-resistant bacteria and persistent biofilms demands innovative therapeutic strategies. To address this urgent challenge, we explore a nanocarrier design strategy that optimizes photosensitizer performance for effective antibacterial phototherapy. Here, we report how the hydrophilic–hydrophobic balance of amphiphilic polymer-based nanocarriers modulates the encapsulation efficiency, photophysical characteristics, and antibacterial efficacy of functionalized zinc phthalocyanine (ZnPc) photosensitizers. Using a series of well-defined diblock copolymers synthesized via RAFT polymerization, we developed micellar nanocarriers with systematically varied lengths of the hydrophilic segment containing quaternized ammonium groups. The resulting functionalized ZnPc-loaded micelles exhibited size-dependent aggregation behavior, with fluorescence lifetimes ranging from 0.13 to 1.57 ns and ROS production shifting between Type I and Type II pathways, depending on the polymer used. Under red-light irradiation (660 ± 20 nm, 10 mW/cm 2, 30 min), ZnPc derivative-loaded micelles achieved up to 5-log reduction in Bacillus subtilis and up to 4-log reduction Escherichia coli viability at 0.1 mg/mL concentration. Fluorescence lifetime measurements upon incubation with bacteria as well as fluorescence lifetime imaging microscopy (FLIM) for solid biofilms revealed microenvironment-dependent modulation of functionalized ZnPc behavior. These findings highlight the critical role of polymer architecture in modulating photophysical properties, which can, however, be altered upon interaction with biological environments.