Logic-based Degradation of Stimuli-Responsive Polymeric Materials

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Non-Technical:Many therapeutic drugs have been successfully developed to treat and cure disease, allowing us to live happier and healthier lives. For these drugs to work as designed, they must reach a specific part of the body with a precise dosage; just as a threshold of medicine is required for successful treatment, drugs that accumulate at unintended bodily locations can have dangerous side effects. To maximize therapeutic efficacy while minimizing harmful side effects, new strategies are needed to selectively target delivery of medications to diseased tissue. The proposed research seeks to establish a generalizable approach to create drug-carrying biomaterials that degrade in response to user-specified combinations of external stimuli. By programming materials to dissolve and release their therapeutic cargo in response to disease-presented cues, this strategy is expected to yield a new class of "smart" drug-delivery platforms with unprecedented versatility. This research will impact education by training multidisciplinary students in polymer chemistry, material science, engineering, and biology through enhanced laboratory and classroom-based courses. Outreach programs centered on biomaterial development and the everyday uses for photochemistry will be created and deployed to introduce and attract under-represented groups to polymer science, sparking diverse student interest and lifelong careers in science, technology, engineering, and math.Technical:The transport of drug- and cell-based therapeutics to diseased sites represents a major barrier to clinical translation. Targeted delivery can be mediated through degradable polymer-based vehicles that utilize disease biomarkers to trigger payload release. The proposed research seeks to establish a modular chemical framework for imparting hydrogel biomaterials with precise degradative responsiveness to multiple environmental cues following user-programmable Boolean logic. By specifying the molecular architecture and connectivity of orthogonal stimuli-labile moieties within material crosslinkers, this project seeks to gain unprecedented specificity over polymer gel dissolution and therapeutic delivery. To illustrate this methodology, seventeen distinct stimuli-responsive materials will be synthesized that collectively yield all possible YES/OR/AND logical outputs from input combinations involving enzyme, reductant, and light. Through systematic studies of crosslinker degradation in response to environmental signals, structure-property relationships of these dynamic material systems as well as a complete understanding of how molecular-scale alterations translate into macroscopic response will be established. The proposed strategies, which will enable unmatched customizability of polymer stimuli-responsiveness, will find great utility throughout several diverse fields including drug delivery, diagnostics, and regenerative medicine. Research efforts will be complemented by the creation of outreach programs centered on photochemistry and biomaterial development.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.