PROJECT SUMMARY Dosing of chemotherapeutics is limited by systemic toxic side effects. We are developing a new class of image-guided, temporarily deployable, endovascular catheter-based medical devices that selectively remove specific drugs from the bloodstream to reduce systemic toxicities. The ChemoFilter platform incorporates specialized sorbent materials that bind target drugs in situ during locoregional therapy. During intraarterial chemotherapy (IAC), including transarterial chemoembolization (TACE) for liver cancer, a substantial fraction of the infused drug passes through the tumor and enters the systemic circulation via the hepatic veins, leading to dose-limiting toxicities, most notably cardiotoxicity from doxorubicin (Dox). The ChemoFilter is designed to be temporarily deployed in the hepatic veins via standard venous access to capture excess drug before it reaches the systemic circulation. The device is removed at the end of the procedure, leaving no implant behind. This project focuses on the development, optimization, and preclinical validation of next-generation ChemoFilter devices that can be reliably delivered and deployed in human hepatic venous anatomy. Prototype devices are designed to accommodate a range of vessel sizes using an expandable filtration architecture, improving clinical usability while maintaining high drug capture efficiency. Devices are evaluated through a combination of benchtop testing, physiologically relevant flow models, and in vivo large animal studies to assess navigability, biocompatibility, and filtration performance. Prototype ChemoFilters will be modeled, built, validated in vitro for efficacy. Preclinical studies will be conducted to quantify the ability of the ChemoFilter to reduce systemic exposure to Dox and decrease drug deposition in non-target organs such as the heart. Additional studies will further evaluate device safety under survival conditions and support design verification, risk analysis, and regulatory readiness. The ChemoFilter technology is broadly applicable to a range of locoregional therapies in oncology and other disease areas where drugs have localized therapeutic effects but systemic toxicities. Successful development of this platform has the potential to significantly improve the safety and efficacy of cancer treatments by enabling higher local drug dosing while minimizing off-target effects.