Materials for drug capture: An approach for removing off-target chemotherapy 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 site-specific delivery, a portion of the chemotherapy dose still enters systemic circulation and causes off-target damage. To address this issue, we are developing materials and devices that are capable of capturing this residual chemotherapy from the blood stream. The ultimate goal is 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 enable 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, whole blood, and initial in vivo studies. 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.