Regulating Stimulus Responses of Functional Materials

Functional materials are materials that are responsive to external stimuli. They appear in natural and synthetic forms and are crucial to the operation of many physical, chemical, and biological systems. An improved understanding and ability to regulate the stimulus responses of functional materials would unleash many insights on the development of novel functional materials and the optimization and application of existing ones. Materials responding to changes in pH and redox conditions are of particular interest to clinical applications owing to the ubiquity with which pH and redox regulation is found in biological systems. We report the development of a pH-responsive virus-like particle (VLP) to better understand the mechanisms behind cellular uptake. The uptake of this pH-responsive VLP by certain cell lines is inhibited by the presence of terminal carboxylic acid moieties attached onto the surface of the VLP. Exposure of the VLP to acidic conditions causes hydrolysis of a linker between the carboxylic acid moieties and the VLP, releasing the carboxylic acid moieties and allowing uptake of the VLP by cells. We also report the development of aminoxyl-based ORCAs for MRI that are able to resist reduction by ascorbate. These ORCAs rely on a macrocycle to encage the aminoxyl radical, shielding the radical from reduction by ascorbate while still allowing the H2O exchange necessary for contrast enhancement. The optimization of these aminoxyl-based ORCAs may someday lead to ORCA designs that can replace gadolinium and other metal-based contrast agents that currently find mainstream clinical usage.