Synthetic networks with tunable responsiveness, biodegradation, and molecular recognition for precision medicine applications

Abstract

Formulations and devices for precision medicine applications must be tunable and multiresponsive to treat heterogeneous patient populations in a calibrated and individual manner. We engineered modular poly(acrylamide-co-methacrylic acid) copolymers, cross-linked into multiresponsive nanogels with either a nondegradable or degradable disulfide cross-linker, that were customized via orthogonal chemistries to target biomarkers of an individual patient’s disease or deliver multiple therapeutic modalities. Upon modification with functional small molecules, peptides, or proteins, these nanomaterials delivered methylene blue with environmental responsiveness, transduced visible light for photothermal therapy, acted as a functional enzyme, or promoted uptake by cells. In addition to quantifying the nanogels’ composition, physicochemical characteristics, and cytotoxicity, we used a QCM-D method for characterizing nanomaterial degradation and a high-throughput assay for cellular uptake. In conclusion, we generated a tunable nanogel composition for precision medicine applications and new quantitative protocols for assessing the bioactivity of similar platforms.