# Alkyltriphenylphosphonium-Functionalized Hyperbranched Polyethyleneimine Nanoparticles for Safe and Efficient Bacterial Eradication: A Structure–Property Relationship Study

## TL;DR

This study explores how modifying polymer nanoparticles can effectively kill bacteria while being safe for human cells.

## Contribution

The study introduces a structure–property relationship approach for designing efficient and safe antibacterial polymers.

## Key findings

- Low-molecular-weight polymers with longer alkyl chains showed high antibacterial efficacy against E. coli and S. aureus.
- SEM images confirmed bacterial membrane disruption and cell death.
- The compounds showed minimal cytotoxicity to mammalian cells.

## Abstract

Polymeric antibacterial agents are attracting attention due to their increased bactericidal efficiency and low probability of causing drug resistance. Their activity, usually attributed to electrostatic interactions and subsequent disruption of cell membranes, is attributed to the number and chemical structure of their functional groups. In this study, hyperbranched polyethyleneimines (PEIs) of two different molecular weights were functionalized with amphiphilic alkyltriphenylphosphonium groups, which are known to induce membrane penetration, especially in cells with high membrane potential. The obtained nanoparticles were chemically and physicochemically characterized, and their inhibition potential against Gram (−) E. coli and Gram (+) S. aureus bacteria was determined. The effects of polymer molecular weight, alkyl chain length, and the number of triphenylphosphonium groups on their antimicrobial efficacy were studied. All compounds exhibited antibacterial properties, especially against S. aureus (MIC < 50 μg/mL). Low-molecular-weight polymeric derivatives and longer alkyl chains proved more efficient against both E. coli (MIC = 20 μg/mL) and S. aureus (MIC = 0.25 μg/mL). SEM images depicted changes in cell morphology, bacterial membrane disruption, and leakage of intracellular contents, signifying loss of cell viability. Minimal cytotoxicity against three mammalian cell lines at relevant antibacterial concentrations demonstrated the potential of a structure–property relationship approach for novel potent antibacterial polymers.