Like the Vikings of old, scientists are hoping a new “longboat” drug delivery system will compromise the walls of resistant cancer cells and fight them with high-dose chemotherapy released only when they are inside.
The new delivery system, detailed in the July issue of the Journal of the American Chemical Society
(JACS), uses soluble, single-walled nanotubes (SWNT) about 50,000 times thinner than a human hair. These longboats, as they are described by researchers, are then tethered with platinum-based chemotherapy drugs similar to those already considered highly effective in fighting testicular and colorectal-based cancers: carboplatin, cisplatin and oxaliplatin. According to the JACS article, although attempts to devise platinum drugs that surpass the anticancer properties of drugs like cisplatin have produced many compounds that display biological activity, only a handful have shown any real promise in clinical trials. “This loss of activity in the body can be associated with poor circulation and delivery to the tumor as well as deactivation mechanisms that irreversibly alter the chemistry of these molecules, particularly those of platinum, rendering them ineffective,” the article reports.
“The key to success in the end is for the platinum not be released before it is delivered to the cell,” Dr. Stephen J. Lippard, a key researcher from the Massachusetts Institute of Technology’s Department of Chemistry in Cambridge, says. Dr. Lippard is currently working on tweaking the chemical makeup of the chemotherapeutic agents so they will adhere to the “oars” of the SWNT longboat and detonate only when they are inside of the cancer cell. The researchers believe when an SWNT-platinum conjugate meets a cancer cell it is pulled inside the cell by endocytosis upon which, in Trojan horse–like fashion, it releases its deadly cargo.
“The nanotubes work because they have unique properties that give them the unique ability to penetrate the cell membrane and deliver their cargo,” Dr. Hongjie Dai of Stanford University’s Department of Chemistry says. “They work with cancer cells as well as T-cells.” The long, skinny shape and surface chemistry of the nanotube seems to be key to its success, Dr. Dai says, “because it binds over the cell for a long length, which is required for uptake.”
Dr. Dai and Dr. Lippard hope this discovery will, unlike the traditional delivery of chemotherapy, spare healthy tissue unaffected by cancer and pave the way for an oral formulation of platinum chemotherapeutic drugs, which are currently delivered intravenously. The SWNT delivery system has already been tested in animal models using doxorubicin and paclitaxel. Both researchers anticipate using SWNT with platinum drugs later this year.