My Bioactive Polymers and Materials Laboratory focuses on the design and synthesis of amphiphilic polymers that can actively interact with cell membranes and use these compounds to understand polymer-lipid interactions as well as to create antimicrobials, polymeric drug carriers and membrane probes.
Non-toxic Antimicrobial Polymers: Membrane Disruption by Amphiphilic Polymers The aim of this project is to develop amphiphilic membrane-disrupting polymers and investigate the mechanism of their antimicrobial activity toward the creation of non-toxic antimicrobials for pharmaceutical applications and biomaterials. The amphiphilic structures of polymers disrupt cell membranes, causing breakdown of the transmembrane potential, leakage of cytoplasmic contents, and ultimately cell death. The cooperative action inherent in polymeric structures enhances this disruption mechanism as compared to small amphiphilic molecules such as surfactants. Synthetic polymers including polymethacrylates, polyacrylamide, and polynorbornenes will be modified with cationic substituents and hydrophobic components. The structure-activity relationship will be studied by varying the chemical structures of polymers, and the antimicrobial mechanism will be investigated using biophysical methods and cellular assays. These studies will provide insight into the design parameters for those polymer structures that display differential lipid-polymer interactions, leading to selective toxicity to bacterial over human cells.
Synthetic Cell-Penetrating Polymers Synthetic amphiphilic polymers will be modified with cationic amine groups and their derivatives to enhance cellular uptake of polymers, mimicking the structure of the natural cell-penetrating HIV-Tat peptide. Translocation across the cell membrane will be investigated to delineate the role of polymer structures including polymer backbones and cationic side chains in the mechanism of internalization. These polymers can be utilized to efficiently deliver protein/peptide drugs, genes, or inorganic particles to both the cytosol and specific organelles.
Conjugated Oligomers as Fluorescent Membrane Probes for Lipid Membranes This project will focus on the design and synthesis of fluorescent membrane probes to examine and characterize lipid membranes. The probes will be prepared using conjugated rigid-rod oligomers, and the partitioning of oligomers to the membranes will be evaluated by physicochemical methods such as fluorescence spectroscopy. The conjugated oligomers that we will design and synthesize will serve as the next generation of fluorescent probes and will allow monitoring of domains in cell membranes by fluorescence techniques and provide insight into these significant membrane structures. These fluorescent probes will be useful tools to increases our knowledge regarding the mechanism of the development of human diseases as well as to create novel diagnostic and therapeutic agents.
Kuroda, K. and DeGrado, W. F. "Amphiphilic polymethacrylate derivatives as antimicrobial agents," J Amer. Chem. Soc., 2005, 127, 4128.
Kuroda, K. and Swager, T.M. "Fluorescent semiconducting polymer conjugates of poly(N-isopropylacrylamide for thermal precipitation assays," Macromolecules 2004, 37, 716.
Kuroda, K. and Swager, T.M. "Synthesis of a nonionic water soluble semiconductive polymer," Chem. Comm. 2003, 26.
Kuroda, K. and Swager, T. M. "Self-amplifying sensory materials: Energy migration in polymer semiconductors," Macromol. Symp. 2003, 201, 127.
Kuroda, K.; Fujimoto, K.; Sunamoto, J. and Akiyoshi, K. "Hierarchical self-assembly of hydrophobically modified pullulan in water: Gelation by networks of nanoparticles," Langmuir 2002, 18, 3780.
Wang, G.Q.; Kuroda, K.; Enoki, T.; Grosberg, A.; Masamune, S.; Oya, T.; Takeoka, Y. and Tanaka, T. "Gel catalysts that switch on and off," P. Natl. Acad. Sci. USA 2000, 97, 9861.