The Reineke group specializes in the synthetic design and investigation of functional macromolecules.

Synthetic materials that are compatible with biological systems are playing an important role in the diagnosis and treatment of many diseases. Consequently, understanding how synthetic materials interact with and affect living systems is one of the most fundamental and important problems in biomedical research. However, little is known about how macromolecules behave, interact, are tolerated, and degraded within the cellular environment. To this end, our research interests seek to elucidate the cellular mechanisms of biomaterial internalization, their function and elimination, and toxicity by designing and synthesizing novel systems to aid our understanding of these phenomena.

Our research efforts are interdisciplinary in nature and encompass the areas of chemistry, materials science, biology and medicine. Students in the Reineke group become familiar with organic, inorganic, and polymer synthesis techniques and materials characterization procedures such as gel permeation chromatography, static and dynamic light scattering, multidimensional NMR, ¹H inversion recovery experiments, transmission electron microscopy, FT-IR, and mass spectrometry. In addition, students with a biomaterials focus routinely gain expertise in gel electrophoresis, confocal microscopy, and cell culture methodologies. Our current research interests are listed below:

                         .........................................

Carbohydrate-Containing Polymers and Dendrimers for Gene Delivery.

With the completion of the human genome, gene-based therapies to treat diseases such as cancer, heart disease, and asthma are becoming increasingly feasible, but gene therapy is still in a very young and experimental stage. Several factors have hindered the development of successful treatments with the first hurdle being the delivery method. In the past, viruses have been used for gene delivery but this delivery technique has presented several problems, for example, viruses can cause immune and inflammatory responses in the body. Our interests lie in the development of nonviral methods of delivering therapeutic DNA. Currently, we are focusing on developing carbohydrate containing polymers and dendrimers that self-assemble with DNA and can deliver genetic material into cultured cells and myocardial tissue in vivo in a nontoxic and effective manner. We are concerned with the design, synthesis, and biological characterization as well as with the examination of the mechanism of toxicity and gene delivery of polymers and dendrimers in cell culture. Two main subprojects in this area focus on: i) elucidating how differences in the chemical structures of polymers and dendrimers affect the biological properties and mechanisms of DNA delivery in vitro, and ii) the delivery of DNA decoys to block NF-ĸB in heart tissue, a transcription factor known to mediate cardiomyocyte death.

                         .....................................................

Glycopolymer-Gd³⁺ Chelates as Novel MRI Contrast Agents.

The early diagnosis of devastating ailments such as heart disease and cancer plays a large role in the successful treatment of disease. An important area of research in disease detection lies in the use of magnetic resonance imaging (MRI), which provides three-dimensional images of deep tissues in a noninvasive manner. Molecular compounds that bind the lanthanide metal gadolinium (Gd³⁺) have traditionally been utilized as magnetic resonance imaging (MRI) contrast agents to increase the resolution of the tissue images because of the high relaxivity that these materials induce on water protons. We are interested in developing polymers that have repeated Gd³⁺ chelates along the backbone. These materials may improve several properties of the molecular materials that are currently in use. Polymeric contrast agents may not only enhance MRI resolution but they may increase the circulation lifetime, reduce toxicity, and enhance the tissue-specific concentration of Gd³⁺. Carbohydrate-based polymers that bind Gd³⁺ are currently being synthesized. We are interested in studying the structure-relaxivity relationships of different polymers and dendrimers via inversion recovery experiments and evaluating toxicity profiles in cell culture. In addition, new methods are being developed to enhance and study tissue-specific uptake of these polymers.

.................................................

Lanthanide-Organic Macrocycles for Anion Sensing.

Anions play essential roles in biological and environmental systems. For example, DNA, amino acids, and a majority of enzyme substrates are anionic or have anionic components. The ability to detect the concentration of specific anions in various media is important for monitoring pollutant levels and studying biological processes. Lanthanide metals, particularly europium (Eu³⁺) and terbium (Tb³⁺), have unique luminescent properties and we are interested in taking advantage of their high sensitivity and long luminescent lifetimes to create macromolecules with sensor properties. Through coordination chemistry, these metals have been linked to chromophoric chelating ligands to create highly luminescent porous molecules with host-guest characteristics. The resulting porous molecules can readily act as sensors because the luminescence intensity of the Eu³⁺ atom is easily altered with the inclusion and binding of anionic guests within the molecular pore. We are interested in the rational design of such macrocyclic compounds for specific anionic analytes and forming a mechanistic understanding of the macrocyle-anion binding and energy-transfer phenomena responsible for the luminescent signaling event.