Design Maps Linking Polymer Architecture and Pharmacokinetics: A Platform for Generalizable Bioimaging - Project Summary. Although medical imaging is indispensable in modern medicine, widely used modalities such as CT, MRI, and PET remain constrained by high costs, radiation exposure, and slow acquisition times, which preclude their use for real-time medical decision-making. Critically, these approaches primarily provide anatomical readouts and are not well-suited for dynamic applications such as intraoperative guidance or functional diagnostics. In contrast, fluorescence imaging is portable, radiation-free, and uniquely capable of delivering real-time molecular feedback, enabling applications that range from surgical navigation to noninvasive monitoring. Recent advances in the second near-infrared (NIR-II) fluorescence window (900 nm – 1200 nm) further enhance this potential, offering deeper tissue penetration, reduced scattering, and suppression of autofluorescence. Despite these advantages, the translation of NIR-II probes has stalled due to the absence of predictive design principles that link polymer structure to pharmacokinetics. Current development is empirical, yielding agents that are either bright but poorly characterized or biocompatible but dim, which limits their clinical and research impact. This MIRA program seeks to establish universal design rules that couple fluorescent polymer architecture with pharmacokinetics, transforming nanoprobe development from ad hoc optimization into a predictive science. By systematically varying polymer topology, molecular weight, and composition, we will generate quantitative design maps that predict both optical performance (brightness, quantum yield, emission stability) and biological fate (clearance route, circulation half-life, organ retention, immune evasion). These principles will be validated across diverse scaffolds and applied to distinct biomedical contexts, including renal diagnostics, vascular imaging, and intraoperative tumor visualization, demonstrating their broad utility. Rather than producing a single probe, the deliverable is a generalizable technology platform that equips the biomedical community with predictive rules and synthetic workflows. This broadly enabling framework will accelerate discovery, expand access to real-time molecular imaging, and directly advance the NIGMS mission to foster foundational tools with wide-ranging impact across biomedicine.
