3D Printed Biosponge Adsorbers for Capturing Toxic Chemotherapy Drugs In Situ in the Body

Cancer is the leading cause of death in most developed nations. Although significant efforts have been made to develop targeted cancer chemotherapy drugs for decades, dosing of chemotherapy drugs is still limited by systematic toxic side effects. To reduce the toxicities of chemotherapy, we have designed a 3D printed biosponge adsorber that can capture the excess untrapped chemotherapy drugs in situ before they circulate throughout the body. Specifically, we focused on liver cancer because of the liver's proximity to the heart with a model drug, doxorubicin (Dox), a highly effective chemotherapy drug with severe cardiac failure risk. Our adsorbers were prepared by forming porous lattice scaffolds via 3D printing and then adding a thin drug (Dox)-adsorbing layer of sulfonated nanostructured block copolymer on the scaffolds. The porous lattices were designed to provide a large surface area for effective drug capture but not to impair the blood flow. The drug-adsorbing block of the polymer layer is polystyrenesulfonate (PSS), which strongly binds to Dox. Using these design parameters, we have successfully placed the adsorbers in the veins downstream of the liver, i.e., the hepatic veins and inferior vena cava (IVC) draining the liver, while the drug (Dox) was injected directly to the liver, mimicking the state-of-the-art, intra-arterial chemotherapy (IAC) procedure for liver cancer patients. Our adsorbers can capture a significant amount of the excess untrapped Dox in situ. The adsorbers can significantly reduce Dox accumulation in the heart (50%) and kidneys (36%) as well as in the surrounding bloodstream (25-45%). Cell viability studies using H9c2 cells confirmed that our adsorbers reduce Dox-induced cardiotoxicity. Additionally, the placement of the adsorbers neither severely impairs the blood flow nor significantly raises blood pressure in the adjacent veins. This confirms the feasibility of the in vivo adsorption approach. Our development poses a potential new route to minimize off-target chemotherapy toxicities and thus help people fight cancer by enabling high-dose locoregional chemotherapy.