Phenylethyl Alcohol-Based Polymeric Nanogels Obtained Through Polymerization-Induced Self-Assembly Toward Achieving Broad-Spectrum Antibacterial Activity

The emergence of bacterial resistance has spurred an urgent need to develop effective alternatives to traditional antibiotics. Phenylethyl alcohol from plants exhibits potential antimicrobial properties, but its efficacy is limited due to its compromised dispersion in water and structural stability in ambient conditions. Herein, for the first time, a polymerization-induced self-assembly strategy was employed to obtain different morphological nanogels with phenylethyl alcohol moieties as hydrophobic cores through in situ reversible addition-fragmentation chain-transfer (RAFT) polymerization. The well-defined copolymers of PTEG_x-<i>co</i>-PPMA_y with controllable molecular weights and narrow polydispersity were confirmed by a combination of techniques. The generated phenylethyl alcohol-based nanogels demonstrated potent antibacterial activity, particularly PTEG₃₀-<i>co</i>-PPMA₇₀ with a one-dimensional linear architecture, which achieved a minimum inhibitory concentration of 62 μg mL^-1 against <i>E. coli</i>. SEM revealed membrane disruption as the bactericidal mechanism, highlighting enhanced efficacy against Gram-negative bacteria due to structural differences in cell envelopes. This study establishes a robust platform for designing phenylethyl alcohol-based nanogels with controllable structures toward achieving potent antimicrobial performance, offering a promising strategy for combating bacterial resistance while addressing the dilemma of conventional antibiotic drug systems.