pH-Sensitive Zwitterionic Polymer as an Antimicrobial Agent with Effective Bacterial Targeting

Abstract

It is highly desirable to develop new and more potent biocompatible antimicrobial agents to reduce the increasing risk of bacterial infection worldwide. To address this problem, we prepared a smart pH-sensitive polymer, poly(N′-citraconyl-2-(3-aminopropyl-N,Ndimethylammonium)ethyl methacrylate), or P(CitAPDMAEMA), which can undergo change in functionality from a biocompatible zwitterionic polymer to an antimicrobial cationic polymer at acidic bacterial infection sites. The precursor polymer, poly(2-(3-aminopropyl-N,Ndimethylammonium)ethyl methacrylate) (P(APDMAEMA)), was first prepared by reversible addition−fragmentation chain transfer (RAFT) polymerization, and then modified with citraconic anhydride to obtain the zwitterionic P(CitAPDMAEMA). P(CitAPDMAEMA) is zwitterionic at physiological pH and exhibits low hemotoxicity and good biocompatibility. However, P(CitAPDMAEMA) can change from neutral to cationic with decreasing pH because of the hydrolysis of citraconic amide under low pH conditions. This switch leads to pronounced bacteria binding of cationic P(CitAPDMAEMA) under acidic conditions of the infection sites and significantly inhibits the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). These results indicate that P(CitAPDMAEMA) is potentially a new on-demand antimicrobial agent.

Quantification of the scratch-healing efficiency for novel zwitterionic polymers

“…Although the materials often have hydrophilic characteristics due to their strong Coulomb interactions, in particular with high-ionic contents, polyzwitterions otherwise behave more like nonionic polymers rather than conventional polyelectrolytes 38,43 . One of the most common applications is zwitterionic hydrogels, which can be responsive to environmental conditions, such as the pH value, temperature or salt content [44][45][46] . It is also possible to combine different effects in one material, such as shape-memory and moisture sensitivity or even selfhealing 44,47,48 .…”

Zwitterionic Polymer-Gated Au@TiO2 Core-Shell Nanoparticles for Imaging-Guided Combined Cancer Therapy

“…Due to their limited interactions with biological proteins 27, 28, they showed excellent biocompatibility and could escape from the reticuloendothelial system, achieving long circulation time 30, 31. We synthesized a pH-sensitive polymer with quaternary ammonium groups according to a previous method 32, which was zwitterionic at physiological pH and was converted to a cationic species in acidic environments. Herein, we loaded doxorubicin (DOX) into the Au@TiO 2 core-shell, then grafted the zwitterionic polymer onto the NP for combined cancer therapy.…”

<p>Recent advances in the treatment of pathogenic infections using antibiotics and nano-drug delivery vehicles</p>

“…Utilizing surface negative charge is one way to target the infection site; however, some pathogens can negate this approach by secreting lactic and acetic acid into the microen-vironment 82. To overcome this problem, several groups have developed surface charge switching polymer micelles and NPs that target the negatively charged cell wall of MRSA at low pH 83,84. Recently, a zwitterionic pH-sensitive polymer, poly (N′-citraconyl-2-(3-aminopropyl N, N dimethylam-monium) ethyl methacrylate) or P(CitAPDMAEMA), was used to inhibit the growth of E. coli and S. aureus under acidic conditions 85.…”