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 PTEGx-co-PPMAy 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-co-PPMA70 with a one-dimensional linear architecture, which achieved a minimum inhibitory concentration of 62 μg mL−1 against E. coli. 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. 1 9 2025 11 9 690 690 27 9 2025 © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/ ). Abstract 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. 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. This urgent clinical challenge necessitates the development of innovative therapeutic strategies incorporating biocompatible, ecologically sustainable antimicrobial agents with minimized off-target toxicity. Phenylethyl alcohol (PA), a plant-based molecule predominantly located in floral species like roses [ 11 ], exhibits potential bactericidal activity, which stems from membrane disruption mechanisms, where it permeates microbial cell barriers and accelerates potassium ion efflux [ 12 ]. In vivo studies further confirm its antioxidative potential [ 13 , 14 ]. In previous studies, phenethyl alcohol was loaded into NLPs using the thin-film hydration method, achieving an encapsulation efficiency of up to 90%, which enhanced its aqueous solubility and utilization efficiency [ 18 ]. However, the NLP encapsulation strategy may be associated with the issues of rapid release and the low release rate of phenethyl alcohol. Polymer nanogels constitute three-dimensional nanoscale networks formed through physical or chemical cross-linking of polymer chains [ 19 ]. The optimized PTEG 30 - co -PPMA 70 copolymer exhibited broad-spectrum bactericidal activity by disrupting cell membranes ( Scheme 1 ). This validates the therapeutic monomer approach as a versatile platform for developing integrated antibacterial nanocarriers with dual carrier–bioactive functions. Scheme 1 Illustration of fabrication procedures of phenylethyl alcohol-based polymeric nanogels and removal of bacteria. 2. Results and Discussion 2.1. Synthesis and Characterization of Phenylethyl Alcohol-Based Polymers The amphiphilic copolymers PTEG 30 - co -PPMA n , characterized by varying molecular weights and controllable molecular structures, were synthesized using reversible addition−fragmentation chain-transfer (RAFT) polymerization, as illustrated in Figure 1 a. Initially, the RAFT polymerization of TEG was employed to create a hydrophilic macromolecular initiator, which played a crucial role in the subsequent polymerization process. The chemical structure of PTEG 30 was confirmed by 1 H NMR spectroscopy. These results demonstrate that the PTEG 30 - co -PPMA 70 nanogel possesses bactericidal capability even against drug-resistant strains. Subsequently, we SEM imaging revealed that the bactericidal mechanism involves disruption of bacterial membrane integrity, leading to cytoplasmic leakage and cell death. The observed disparity in activity between Gram-negative and Gram-positive species suggests potential selectivity influenced by differences in cell wall structure. Furthermore, while its antibacterial activity is slightly lower than that of the conventional antibiotic norfloxacin, no statistically significant difference was observed. Additionally, the nanogel exhibited excellent biocompatibility. This study not only advances the understanding of structure–property relationships in amphiphilic copolymers but also provides a versatile platform for designing functional nanogels with tailored antimicrobial properties. Future work should focus on optimizing polymer architectures for targeted applications and exploring synergistic effects with conventional antibiotics to broaden their therapeutic potential. 4. Materials and Methods 4.1. Materials Tetraethylene glycol (99%), phenethyl alcohol (PMA, Analytical Reagent, AR), triethylamine (TEA, AR), and iodine (I 2 99%) were obtained from Aladdin (Shanghai, China).

Surgical site infection (SSI) is the most common postoperative complication and substantially increases health-care costs. Published meta-analyses and international guidelines differ with regard to which preoperative skin antiseptic solution and concentration has the highest efficacy. We aimed to compare the efficacy of different skin preparation solutions and concentrations for the prevention of SSIs, and to provide an overview of current guidelines. This systematic review and network meta-analysis compared different preoperative skin antiseptics in the prevention of SSIs in adult patients undergoing surgery of any wound classification. We searched for randomised controlled trials (RCTs) in MEDLINE, Embase, and Cochrane CENTRAL, published up to Nov 23, 2021, that directly compared two or more antiseptic agents (ie, chlorhexidine, iodine, or olanexidine) or concentrations in aqueous and alcohol-based solutions. We excluded paediatric, animal, and non-randomised studies, and studies not providing standard preoperative intravenous antibiotic prophylaxis. Studies with no SSIs in both groups were excluded from the quantitative analysis. Two reviewers screened and reviewed eligible full texts and extracted data. The primary outcome was the occurrence of SSI (ie, superficial, deep, and organ space). We conducted a frequentist random effects network meta-analysis to estimate the network effects of the skin preparation solutions on the prevention of SSIs. A risk-of-bias and Grading of Recommendations, Assessment, Development, and Evaluation assessment were done to determine the certainty of the evidence. This study is registered with PROSPERO, CRD42021293554. Overall, 2326 articles were identified, 33 studies were eligible for the systematic review, and 27 studies with 17 735 patients reporting 2144 SSIs (overall incidence of 12·1%) were included in the quantitative analysis. Only 2·0-2·5% chlorhexidine in alcohol (relative risk 0·75, 95% CI 0·61-0·92) and 1·5% olanexidine (0·49, 0·26-0·92) significantly reduced the rate of SSIs compared with aqueous iodine. For clean surgery, we found no difference in efficacy between different concentrations of chlorhexidine in alcohol. Seven RCTs were at high risk of bias, 24 had some concerns, and two had low risk of bias. Heterogeneity across the studies was moderate (I2=27·5%), and netsplitting did not show inconsistencies between direct and indirect comparisons. Five of ten studies that mentioned adverse events related to the skin preparation solutions reported no adverse events, and five reported a total of 56 mild events (mainly erythema, pruritus, dermatitis, skin irritation, or mild allergic symptoms); none reported a substantial difference in adverse events between groups. For adult patients undergoing a surgical procedure of any wound classification, skin preparation using either 2·0-2·5% chlorhexidine in alcohol or 1·5% olanexidine is most effective in the prevention of SSIs. For clean surgery, no specific concentration of chlorhexidine in alcohol can be recommended. The efficacy of olanexidine was established by a single randomised trial and further investigation is needed. Dutch Association for Quality Funds Medical Specialists.