Porous Nanoparticles Deliver Drug Cocktails to Tumors
Melding nanotechnology and medical research, researchers from Sandia National Laboratories, the University of New Mexico, and the UNM Cancer Research and Treatment Center have produced an effective strategy that uses nanoparticles to treat tumors with a mélange of anticancer agents. This strategy relies on using silica nanoparticles honeycombed with cavities that can store large amounts and varieties of drugs loaded inside a lipid-based nanoparticle known as a liposome.
"The enormous capacity of the nanoporous core, with its high surface area, combined with the improved targeting of an encapsulating lipid bilayer, permits a single 'protocell' loaded with a drug cocktail to kill a drug-resistant cancer cell," says team leader Jeff Brinker, who is the co-principal investigator of the University of New Mexico Cancer Nanotechnology Platform Partnership. "That's a millionfold increase in efficiency over comparable methods employing liposomes alone — without nanoparticles — as drug carriers." Dr. Brinker and his team published the results of their work in the journal Nature Materials.
The nanoparticles and the surrounding cell-like membranes formed from liposomes create what the researchers call a protocell: the membrane seals in the deadly cargo and is modified with targeting molecules that bind specifically to receptors overexpressed on the cancer cell's surface. The nanoparticles provide stability to the supported membrane and release the therapeutic cargo within the cell.
A current Food and Drug Administration-approved nanoparticle delivery strategy is to use liposomes themselves to contain and deliver the cargo. In a head-to-head comparison of targeted liposomes and protocells with identical membrane and peptide compositions, Dr. Brinker and colleagues report that the greater cargo capacity, stability, and targeting efficacy of protocells leads to a drug formulation that is much more effective at killing human liver cancer cells.
Another advantage to protocells over liposomes alone is that it is far easier to load drugs into the porous nanoparticles than it is with liposomes. Loading drugs into liposomes requires complex strategies that boost the cost of making those formulations. In contrast, loading the porous nanoparticles can be done by simply soaking the nanoparticles in a drug solution. The liposome then serves as a shield that restricts toxic chemotherapy drugs from leaking from the nanoparticle until the protocell binds to the cancer cell. This means that only low levels of anticancer agents, at most, escape into the blood stream or attack other cells.
This work, which is detailed in a paper titled, "The targeted delivery of multicomponent cargos to cancer cells by nanoporous particle-supported lipid bilayers," was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's Web site.