Tackling cancer with chemotherapeutics is a careful balancing act between killing the tumor and preserving the health of other tissues. Indeed, the side effects of some chemotherapeutic agents can be so severe that the desired dose for eradicating a tumor is unusable.
Researchers are therefore working to find ways to maximize dose while minimizing systemic toxicity. One approach currently in clinical trials is to divert blood after it flows through an organ targeted with localized high-dose chemotherapy and send it through a filtration device before the medication can flow to the rest of the body. However, this is an invasive approach and requires the subsequent monitoring of a patient in an intensive care unit.
In search of a more benign procedure, Steven Hetts of the University of California, San Francisco, and colleagues are developing in-vein approaches to capture drugs as they exit the treated organ. One method, reported last summer, involves capturing drugs with DNA-coated iron oxide nanoparticles attached to magnets inserted into the vein. Their latest approach uses a tubular lattice structure coated with a drug-binding material.
The tube is made from biocompatible poly(ethylene glycol) diacrylate (PEGDA), which is 3D printed to form a 5 mm diameter, 30 mm long cylinder with an internal lattice and a central lumen for a guide wire. The structure is then coated with a copolymer that tightly binds the drug doxorubicin—a commonly used chemotherapeutic whose side effects with increasing dosage include irreversible heart damage.
Proof-of-principle tests showed that when placed in the iliac vein in the lower abdomen of live pigs, the device effectively captured more than two-thirds of the doxorubicin infused a short distance upstream. The drug did not pass through an organ in these experiments, so whether it would work in that setting, reduce side effects, and be safe for humans is still unknown.
“It’s still experimental and far away from prime time . . . but the idea is very clever,” says Krishna Kandarpa of the National Institute of Biomedical Imaging and Bioengineering, who was not involved in the research. “It’s definitely worth pursuing and doing it for other drugs.” (ACS Cent Sci, doi: 10.1021/acscentsci.8b00700, 2019; Nat Commun, 9:2870, 2018)
|Drug capturing approach||In-vein device||Useful for||Drugs tested||Capture rates|
|Magnetic nanoparticles||25 cylindrical magnets coated with DNA-loaded iron nanoparticles and strung together on a wire||Potentially any DNA-binding drug||Doxorubicin, Cisplatin and Epirubicin||Cisplatin: 20% from phosphate-buffered saline Epirubicin: 68% from human serum in vitro Doxorubicin: 93% from human serum in vitro; 82% from blood in live pigs|
|3D-printed absorber||3D-printed lattice tube made of poly(ethylene glycol) diacrylate and coated with a negatively charged copolymer||Potentially any positively charged drug||Doxorubicin||Doxorubicin: 69% from blood in live pigs|