Accelerated Materials Discovery Using Chemical Informatics Investigation of Polymer Physicochemical Properties and Transgene Expression Efficacy.

Quantitative approaches to structure-property relationships are critical for the accelerated design and discovery of biomaterials in biotechnology and medicine. However, the absence of definitive structures, unlike those available for small molecules or 3D crystal structures available for some proteins, has limited the development of Quantitative Structure-Property Relationship (QSPR) models for investigating physicochemical properties and biological activity of polymers. In this study, we describe a combined experimental and cheminformatics paradigm for first developing QSPR models of polymer physicochemical properties, including molecular weight, hydrophobicity, and DNA-binding activity. Quantitative Structure-Activity Relationship (QSAR) models of polymer-mediated transgene expression were then developed using these physicochemical properties with an eye towards developing a novel two-step chemical informatics paradigm for determining biological activity (e.g., transgene expression) of polymer properties as related to physicochemical properties. We also investigated a more conventional approach in which biomaterial efficacy, i.e., transgene expression activity, was directly correlated to structural representations of the polymers used for delivering plasmid DNA. Our generalized chemical informatics approach can accelerate the discovery of polymeric biomaterials for several applications in biotechnology and medicine, including in nucleic acid delivery.

Investigation into Pseudo-Capacitance Behavior of Glycoside-Containing Hydrogels.

Electrochemical pseudocapacitors are an attractive choice for energy storage applications because they offer higher energy densities than electrostatic or electric double layer capacitors. They also offer higher power densities in shorter durations of time, as compared to batteries. Recent efforts on pseudocapacitors include biocompatible hydrogel electrolytes and transition metal electrodes for implantable energy storage applications. Pseudocapacitive behavior in these devices has been attributed to the redox reactions that occur within the electric double layer, which is formed at the electrode-electrolyte interface. In the present study, we describe a detailed investigation on redox reactions responsible for pseudocapacitive behavior in glycoside-containing hydrogel formulations. Pseudocapacitive behavior was compared among various combinations of biocompatible hydrogel electrolytes, using carbon tape electrodes and transition metal electrodes based on fluorine-doped tin oxide. The hydrogels demonstrated a pseudocapacitive response only in the presence of transition metal electrodes but not in the presence of carbon electrodes. Hydrogels containing amine moieties showed greater energy storage than gels based purely on hydroxyl functional groups. Furthermore, energy storage increased with greater amine content in these hydrogels. We claim that the redox reactions in hydrogels are largely based on Lewis acid-base interactions, facilitated by amine and hydroxyl side groups along the electrolyte chain backbones, as well as hydroxylation of electrode surfaces. Water plays an important role in these reactions, not only in terms of providing ionic radicals but also in assisting ion transport. This understanding of redox reactions will help determine the choice of transition metal electrodes, Lewis acid-base pairs in electrolytes, and medium for ionic transport in future biocompatible pseudocapacitors.

A Colorimetric Plasmonic Nanosensor for Dosimetry of Therapeutic Levels of Ionizing Radiation.

Modern radiation therapy using highly automated linear accelerators is a complex process that maximizes doses to tumors and minimizes incident dose to normal tissues. Dosimeters can help determine the radiation dose delivered to target diseased tissue while minimizing damage to surrounding healthy tissue. However, existing dosimeters can be complex to fabricate, expensive, and cumbersome to operate. Here, we demonstrate studies of a liquid phase, visually evaluated plasmonic nanosensor that detects radiation doses commonly employed in fractionated radiotherapy (1-10 Gy) for tumor ablation. We accomplished this by employing ionizing radiation, in concert with templating lipid surfactant micelles, in order to convert colorless salt solutions of univalent gold ions (Au(1)) to maroon-colored dispersions of plasmonic gold nanoparticles. Differences in color intensities of nanoparticle dispersions were employed as quantitative indicators of the radiation dose. The nanoparticles thus formed were characterized using UV-vis absorbance spectroscopy, dynamic light scattering, and transmission electron microscopy. The role of lipid surfactants on nanoparticle formation was investigated by varying the chain lengths while maintaining the same headgroup and counterion; the effect of surfactant concentration on detection efficacy was also investigated. The plasmonic nanosensor was able to detect doses as low as 0.5 Gy and demonstrated a linear detection range of 0.5-2 Gy or 5-37 Gy depending on the concentration of the lipid surfactant employed. The plasmonic nanosensor was also able to detect radiation levels in anthropomorphic prostate phantoms when administered together with endorectal balloons, indicating its potential utility as a dosimeter in fractionated radiotherapy for prostate cancer. Taken together, our results indicate that this simple visible nanosensor has strong potential to be used as a dosimeter for validating delivered radiation doses in fractionated radiotherapies in a variety of clinical settings.