Materials for drug capture: Filtering off-target chemotherapy agents from the bloodstream

Abstract

The systemic, off-target toxicity of chemotherapy is a well-known problem in oncol. In an effort to overcome this challenge, many approaches have been developed to deliver chemotherapy directly and exclusively the tumor. One of these approaches is transarterial chemoembolization (TACE), a procedure in which chemotherapy is introduced via catheter directly into the artery supplying the tumor. Despite this sitespecific delivery, a portion of the chemotherapy dose still enters systemic circulation and causes off-target damage. To address this issue, we are developing materials that are capable of capturing this residual chemotherapy from the blood stream. Ultimately, this material will be used to construct a device that can be deployed via catheter "downstream" from the tumor, enabling excess chemotherapy to be sequestered before entering systemic circulation. Our approach uses DNA-functionalized surfaces, which enables the capture of DNA-targeting chemotherapy drugs. In order to improve the cost and scalability of this system, we developed simple methods of covalently attaching genomic DNA to a variety of surfaces. We have further demonstrated that this approach is capable of sequestering doxorubicin, cisplatin, and epirubicin-three common chemotherapy agents-from soln. at clin. relevant concns. The efficacy of these materials was demonstrated in PBS, human serum, and blood, indicating that this approach is likely viable in vivo. Moreover, the kinetics of drug capture are rapid: We obsd. >95% redn. of doxorubicin concn. in human serum in <10 min. The efficacy of these materials indicates that drug capture is indeed a viable strategy for mitigating the harmful side-effects assocd. with chemotherapy.