RESEARCH
BACKGROUND
Antibiotic-resistant bacteria have been a significant concern to medical practice, diminishing the number of available treatment options by antibiotics. There is a compelling need to establish new antimicrobials that are active against antibiotic-resistant bacteria without contributing to emergent resistance development. Our laboratory focuses on a new molecular design of antimicrobial synthetic polymers with alternative mode of antibacterial action for multiple applications including pharmaceutical agents, antimicrobial coatings on catheters and implants, and dental composite fillings.
ANTIMICROBIAL PEPTIDE-MIMETIC POLYMERS
To create new antimicrobial materials effective to drug resistant bacteria, our laboratory has developed the molecular mimicry of naturally occurring antimicrobial peptides using synthetic methacrylate polymers. These polymers are designed to mimic the cationic functionality and amphiphilic nature of antimicrobial peptides to act as membrane-active antimicrobial agents. These antimicrobial polymers represent the hallmarks of antimicrobial peptide such as antimicrobial activity against a broad spectrum of bacteria including antibiotic-resistant strains, low propensity for resistance development in bacteria, and no adverse toxicity against host cells.
ANTICANCER POLYMERS FOR TARGETING DORMANT CANCER CELLS
Metastases are a major cause of death in prostate cancer patients. Metastases are largely the result of the reactivation of disseminated tumor cells (DTCs) which escaped the primary tumor early in disease progression, yet have remained dormant for years. Significantly, DTCs are largely resistant to conventional chemotherapies, which target actively proliferating cells. Accordingly, a new strategy must be developed to target and treat dormant cancer cells. To that end, we design and engineer novel peptide-mimetic polymers targeting cancer cell membranes with an ultimate goal of developing anticancer therapeutics effective in killing dormant cancer cells. We will exploit non-peptide polymer scaffolds to mimic small amphiphilic anticancer peptides (ACPs). ACPs bind to anionic lipids exposed on cancer cell surfaces by electrostatic interaction, imparting cancer-selective toxicity. The bound ACPs disrupt the cell membrane to cause cell death, which is not dependent on cell proliferation. This new strategy can be used in conjunction with conventional therapies, or when conventional therapies fail.
ANTI-BIOFILM COATINGS
Bacteria proficiently adhere to synthetic surfaces of medical devices or implants, and establish matrix-encased bacterial communities, known as biofilms. This biofilm formation is a concern because the biofilm matrix protects resident bacteria from host-defense mechanisms and antibiotic challenges, resulting in chronic and recurrent bacterial infections. To prevent the biofilm formation, our laboratory has developed versatile polymeric materials for bactericidal or anti-fouling coatings by utilizing a mussel protein mimetic adhesive group or a star-shaped polymer nano-architecture.
BIOMIMETIC DENTAL ADHESIVES FOR CONTAMINATED SURFACES
In the dental bonding procedure, isolation of the area to be bonded from oral fluids is essential for high bonding quality. However, preventing oral fluid contamination completely under clinical conditions is frequently difficult because of the natural wetness of the oral environment. We have developed a synthetic polymer functionalized with catechol groups as dental adhesives for wet dentin surfaces, potentially eliminating the complications associated with saliva contamination. This synthetic polymer mimics mussel adhesive proteins that enable mussels to anchor to a variety of wet surfaces. We demonstrated that the new polymer combined with an Fe3+ additive improved bond strength of a commercial dental adhesive to artificial saliva contaminated dentin surface.
