165196-44-1Relevant articles and documents
Rational Design of Single-Chain Polymeric Nanoparticles That Kill Planktonic and Biofilm Bacteria
Nguyen, Thuy-Khanh,Lam, Shu Jie,Ho, Kitty K. K.,Kumar, Naresh,Qiao, Greg G.,Egan, Suhelen,Boyer, Cyrille,Wong, Edgar H. H.
, p. 237 - 248 (2017)
Infections caused by multidrug-resistant bacteria are on the rise and, therefore, new antimicrobial agents are required to prevent the onset of a postantibiotic era. In this study, we develop new antimicrobial compounds in the form of single-chain polymeric nanoparticles (SCPNs) that exhibit excellent antimicrobial activity against Gram-negative bacteria (e.g., Pseudomonas aeruginosa) at micromolar concentrations (e.g., 1.4 μM) and remarkably kill ≥99.99% of both planktonic cells and biofilm within an hour. Linear random copolymers, which comprise oligoethylene glycol (OEG), hydrophobic, and amine groups, undergo self-folding in aqueous systems due to intramolecular hydrophobic interactions to yield these SCPNs. By systematically varying the hydrophobicity of the polymer, we can tune the extent of cell membrane wall disruption, which in turn governs the antimicrobial activity and rate of resistance acquisition in bacteria. We also show that the incorporation of OEG groups into the polymer design is essential in preventing complexation with proteins in biological medium, thereby maintaining the antimicrobial efficacy of the compound even in in vivo mimicking conditions. In comparison to the last-resort antibiotic colistin, our lead agents have a higher therapeutic index (by ca. 2-3 times) and hence better biocompatibility. We believe that the SCPNs developed here have potential for clinical applications and the information pertaining to their structure-activity relationship will be valuable toward the general design of synthetic antimicrobial (macro)molecules.
Multi-modal detection of colon malignancy by NIR-tagged recognition polymers and ultrasound contrast agents
Bloch, Meital,Jablonowski, Lauren,Yavin, Eylon,Moradov, Dorit,Djavsarov, Irena,Nyska, Abraham,Wheatley, Margaret,Rubinstein, Abraham
, p. 504 - 516 (2015)
To increase colonoscopy capability to discriminate benign from malignant polyps, we suggest combining two imaging approaches based on targeted polymeric platforms. Water-soluble cationized polyacrylamide (CPAA) was tagged with the near infrared (NIR) dye IR-783-S-Ph-COOH to form Flu-CPAA. The recognition peptide VRPMPLQ (reported to bind specifically to CRC tissues) was then conjugated with the Flu-CPAA to form Flu-CPAA-Pep which was then incorporated into echogenic microbubbles (MBs) made of polylactic acid (PLA) that are highly responsive to ultrasound. The ultimate design includes intravenous administration combined with local ultrasound and intra-colon inspection at the NIR range. In this proof of principle study PLA MBs were prepared by the double emulsion technique and loaded with several types of Flu-CPAA-Pep polymers. After insonation the submicron PLA fragments (SPF)-containing Flu-CPAA-Pep were examined in vitro for their ability to attach to colon cancer cells and in vivo (DMH induced rat model) for their ability to attach to colon malignant tissues and compared to the specific attachment of the free Flu-CPAA-Pep. The generation of SPF-containing Flu-CPAA-Pep resulted in a tissue attachment similar to that of the free, unloaded Flu-CPAA-Pep. The addition of VRPMPLQ to the polymeric backbone of the Flu-CPAA reduced cytotoxicity and improved the specific binding.
Towards Sequence-Controlled Antimicrobial Polymers: Effect of Polymer Block Order on Antimicrobial Activity
Judzewitsch, Peter R.,Nguyen, Thuy-Khanh,Shanmugam, Sivaprakash,Wong, Edgar H. H.,Boyer, Cyrille
, p. 4559 - 4564 (2018)
Synthetic polymers have shown promise in combating multidrug-resistant bacteria. However, the biological effects of sequence control in synthetic antimicrobial polymers are currently not well understood. As such, we investigate the antimicrobial effects o
Effect of Hydrophobic Groups on Antimicrobial and Hemolytic Activity: Developing a Predictive Tool for Ternary Antimicrobial Polymers
Phuong, Pham Thu,Oliver, Susan,He, Junchen,Wong, Edgar H. H.,Mathers, Robert T.,Boyer, Cyrille
, p. 5241 - 5255 (2020/11/30)
Antimicrobial polymers have emerged as a potential solution to the growing problem of antimicrobial resistance. Although several studies have examined the effects of various parameters on the antimicrobial and hemolytic activity of statistical copolymers,
