Technology Offers New Treatment for Toxin Exposure and Drug Delivery
In a joint effort, the Argonne National Laboratory, the Armed Forces Radiobiology Research Institute, and The University of Chicago Hospitals are developing biodegradable nanospheres to clean the blood of victims of radiological, chemical, and biological terrorist attacks. The technology also shows promise for delivering therapeutic drugs to targeted cells and organs.
The system uses components approved by the U.S. Food and Drug Administration and a novel approach to magnetic filtration that will directly remove toxic agents from the bloodstream. The technology could be extended to other medical conditions such as drug and medication overdose emergencies or treatment of chronic or acute illnesses.
Key to the technology is biodegradable nanospheres 100 to 5,000 nanometers in diameter that are small enough to pass through tiny blood vessels, yet large enough to avoid being filtered from the bloodstream by the kidneys. One nanometer is one millionth of a meter–about 70,000 times smaller than the diameter of an average human hair.
The particles contain a magnetic iron compound and are coated with a type of polyethylene glycol that prevents white blood cells from attacking them. Attached to the particles’ surfaces are proteins that bind to specific toxic agents. Intravenously injected into the patient, the nanospheres circulate through the bloodstream, where their surface proteins bind to the targeted toxins.
After the nanospheres have collected the toxins, they are removed from the bloodstream via a small, dual-channel shunt inserted into an arm or leg artery. The shunt circulates the blood through an external magnetic separator, where strong magnets immobilize the iron-based particles. Clean blood flows out of the separator and back into the bloodstream.
The system offers a number of advantages over existing methods to clean human blood of radioactive and other hazardous materials. Current medical procedures to detoxify human blood are restricted to a few types of toxins and are mainly limited to dialysis and filtration.
In addition, currently available treatments can take several hours to complete, require the turnover and filtration of large volumes of blood, are inefficient at removing toxins, and can be risky for the patient. For these reasons, current methods are restricted to patients with kidney failure and certain types of drug overdoses.
Alternative treatments, such as antibodies and chelators that combine with and neutralize toxins, can be used for specific kinds of toxins, but they are inefficient and can cause serious side effects, such as allergic reactions and organ failure.
Nanosphere technology also is being developed to deliver drugs, genes, and otherwise undeliverable therapies–such as acutely toxic small molecules, peptides, and pharmaceutics–to targeted cells and organs. The particle surfaces can be designed to provide receptor-mediated targeting of cells, sustained drug delivery, or magnetic targeting of organs. The nanospheres can deliver water-based or oil-based drugs.
Potential applications include: biological toxin exposures; radiological toxin exposure and radioprotection; internal hemorrhage; brain swelling; stroke therapy; cancer therapy; and acute trauma leading to kidney failure.
The project has developed a prototype magnetic filter, has tested many nanospheres formulations for specific toxins, and is conducting ongoing trials in vitro and in vivo.