New nanomaterials are overcoming limitations of CNTs to advance drug research.
Nanotechnology has proven to be a strong driver for medical applications, with drug delivery overwhelming all other areas. The whole technology arena has evolved from loading nanoparticles with compounds used to fight diseases just a few years ago to the current use of carbon nanotubes (CNTs) and other nanostructures as carriers for drugs that can penetrate cell walls and even the cell nucleus itself.
The question of toxicity
New nanomaterials, like nanohorns (CNHs), nanosponges, and nanodiamonds have recently surfaced that bypass the limitations of earlier nanomaterials.
The quite visible limitation and oft-times driver of these technology advances is the still-undefined toxicity of all nanomaterials. Development of the CNH drug delivery mechanisms, for example, was mostly driven by the suspected, but still uncharacterized, nanotoxicity of CNTs in animal studies.
The early discovery of CNTs and their wide range of excellent physical properties led to their selection for drug delivery. CNTs can carry significant amounts of medicinal materials within their structures and then translocate through plasma membranes in a manner resembling cell-penetrating peptides. Over the past few years, several research groups have demonstrated the ability of both single-walled CNTs (SWCNTs) and multi-walled CNTs to move inside a variety of cell types and deliver both therapeutic and diagnostic small molecules to the cells.
Testing of SWCNTs in rats, however, has found them to have a pulmonary toxicity in an aerosolized form that is likely due to the use of metallic catalysts in their preparation, that are then retained in the completed nanostructure. Researchers at a number of locations, including Tiajin Univ., China; Oak Ridge National Laboratory, Tenn.; and the Univ. of Tennessee, Nashville, have created CNHs without the use of metallic catalysts, thereby eliminating the toxicity problem shown by CNTs.
New shapes emerge
CNH has a structure similar to a CNT except that it’s closed at one end in a cone-shaped cap, or horn. Strong van der Waals forces in the CNHs drive them to self-assemble into spherical dahlia flower-like assemblies with the horn ends sticking out in all directions. The <100 nm dia CNH assembly has a tendency to agglomerate into clusters. Surfaces of the CNHs can be modified with gum arabic and natural polysaccharide to improve their biocompatibility. The Tiajin Univ. researchers have incubated CNHs with HeLa (cancer) cells and found them inside the cellular membranes, but not the nucleus. The overall size of the CNH is too large to navigate the smaller (~ 40 nm dia) nuclear pore complex.
Researchers at Vanderbilt Univ., Nashville, Tenn., have created a nanosponge structure for drug delivery. Eva Harth, assistant professor of chemistry, created a nanoparticle that uses extensive internal cross-linking to compress a long, linear carbon molecule into a sphere just 10 nm in diameter. The resulting nanosponge is about the size of a protein and can be used to attach and hold a large number of drug molecules, which, with its small size, can reach a cell’s nucleus. The nanosponge can also be used as a transporter to deliver large molecules into specific sub-cellular locations.
Researchers at Northwestern Univ., Evanston, Ill., have recently announced the development of yet another nano-enabled method of drug delivery. Dean Ho, assistant professor of biomedical engineering, led this research which created nanodiamonds. The nanodiamonds, each only 2 nm in dia., form aggregated clusters from 50 to 100 nm in dia. Drugs can be loaded onto the surface of the individual diamonds, but they are inactive when the diamonds are aggregated. The drugs only become active when the cluster reaches its target, breaks apart, and slowly releases the drug. This structure, with its large surface area, can carry up to five times as much drug as other methodologies. Nanodiamonds are also soluble in water, extremely stable, and allow a wide range of chemistry to be performed on their surfaces, further broadening their functionalization capabilities for specific applications.
Ho’s research, funded by the NIH’s National Institute of Allergy and Infectious Diseases, has already demonstrated the nanodiamond’s ability to deliver anticancer drugs inside of a variety of cancer cells, break up within the cell, and slowly release the drug.
Clearly, nano-structured materials are getting a large amount of attention in the drug delivery arena due to their ability to transport drug compounds into the hearts of individual cells. Toxicity issues still need to be clarified and characterized, as little is known about the quantities of nanomaterials retained within biological materials and their effects on them.
