Abstract
Chemotherapy is the major treatment option for cancer patients. However, systemic toxicity from
these drugs can significantly impact patient's quality of life and overall survival. Prevention and
effective management of side effects of chemotherapy drugs represents a significant bottleneck in
oncology today. Many drugs in Phase I trials have been abandoned and many patients have been
denied hope from promising treatment regimens because of the associated adverse systemic side
effects (4). Furthermore, toxicity from FDA-approved drugs, like interleukin-2, have prevented their
use despite having efficacy. To address these limitations of chemotherapy, we propose a
transformative technology where the chemotherapy drug is intra-arterially infused from a drug-
eluting stent (DES) and captured along the venous outflow of the tumor using an intravascular
drug-capturing device (DCD). We believe that by using the DES/DCD pair system, the tumor site
will receive highly localized chemotherapy while systemic presence of the excessive drug molecules
will be minimized or eliminated (Fig. 1). This strategy can be applied to many cancers, i.e., internal
iliac vein/artery for pelvic tumors, bronchial artery/pulmonary vein for lung cancers, internal mammary
vein/artery for breast cancer. In this proposal, we will focus on liver cancer because of our liver
angiography experience, the liver has a dual blood supply, liver vasculature is large enough to
accommodate stent placements and lower cost of imaging, experimentation and maintaining rabbits.
As proof of principle, we will use liver cancer as a model to demonstrate the efficacy of this novel
strategy, by delivering DNA-targeting anti-cancer drug doxorubicin, which naturally fluoresces at 480
nm allowing easy detection and quantification. Our preliminary data demonstrates exciting results
showing our capability in fabrication of anti-thrombotic biomaterials that can selectively release and
capture drug molecules. In addition, we have rich experience in catheter-based delivery of
biomaterials for a number of in vivo applications, which will ensure successful completion of the
proposed project. First we will develop the DES (Aim 1), then develop the DCD (Aim 2) and finally
test the drug release and capture concept in rat and rabbit animal models (Aim 3). Successful
development of such a system will represent a paradigm shift in the oncology community by
improving patient's quality of life, potentially prolonging survival, resurrecting failed Phase I
trials from drug toxicity, increasing the use of FDA-approved previously toxic drugs, and
opening up new clinical trials to test much higher doses. The proposed idea of drug release and
capture represents a platform technology and may have unparalleled impact in other diseases. For
example, the system can be designed to isolate exposure to thrombolytic therapy or
immunosuppressants.