Mar 27, 2009
Nanoparticles: image, target, treat
Nanoparticles – in their myriad of shapes and forms – are touted as ideal for a broad range of cancer-management applications. In a hotbed of research activity, nanoscale-materials are being developed to image the distribution of tumour cells in the body, target and attach to cancerous cells, destroy unwanted cells via ablation or delivering drugs, or – according to the latest claims – all of the above. Here, we take a look at some of the new nanotechnology developments reported over the last few weeks.
First up, a US research team is using hollow gold nanospheres to enhance the cell-killing effects of photothermal ablation. The ultimate aim: to develop a minimally invasive treatment for malignant melanoma. The researchers equipped the nanospheres with a protein fragment that targets melanoma cells while avoiding healthy skin cells. When exposed to near-infrared light, which penetrates deeply through the skin, the nanospheres heat up and destroy the cancer cells.
In recent studies in mice, the hollow nanospheres did eight times more damage to skin tumours than the same particles without the targeting peptides. They're also claimed to be 50 times more effective than solid gold nanoparticles for photothermal therapy.
With sizes ranging from 30 to 50 nm, the nanoshells are much smaller than other nanoparticles previously designed for photoablation therapy. Another benefit is that gold is safer than other metal nanoparticles for use in the body. The next stage will be to test the nanospheres in humans. Though with the need for extensive preclinical toxicity studies, there's some way to go yet before the technique could find its way into clinical practice.
The researchers, from the University of California Santa Cruz, the University of California Berkeley, and the MD Anderson Cancer Center in Houston, TX, presented this work at the American Chemical Society's 237th National Meeting, held this week in Salt Lake City, UT.
As well as using nanoparticles to kill cells directly, they can also function as effective drug-delivery vehicles. In particular, the development of targeted nanoparticles that locate in particular organs or cancerous cells could help minimize the often extreme side-effects associated with many chemotherapy regimes.
For example, quantum dots coated with certain sugar molecules accumulate selectively in specific tissues and organs, enabling them to deliver anti-cancer drugs to the target region without causing body-wide side-effects. That's the conclusion of research from the Swiss Federal Institute of Technology (ETH) in Zurich (J. Am. Chem. Soc. 131 2110).
In a study with laboratory mice, the ETH Zurich scientists coated quantum dots with either mannose or galactosamine, two sugars that accumulate selectively in the liver. The sugar-coated dots became three times more concentrated in the mice livers than the regular dots, demonstrating their higher specificity.
Chemists at Brown University (Providence, RI), meanwhile, have come up with a means for delivering the cancer-fighting drug cisplatin directly to tumour cells in breast-cancer patients. The researchers created a dumbbell-like twin nanoparticle by attaching a gold nanoparticle to an iron-oxide nanoparticle. They then coupled a synthetic antibody (Herceptin) to the iron-oxide end and coupled cisplatin to a ligand attached to the gold nanoparticle (J. Am. Chem. Soc. 131 4216).
The Herceptin binds to a protein located on the surface of HER-2-positive tumour cells (HER2 is a protein that's over-expressed in certain breast cancers). The targeted nanoparticle can then unload cisplatin directly into the malignant cell. The use of a pH-sensitive covalent bond to connect the gold nanoparticle to the cisplatin ensures that the drug is not released prematurely into the body but remains attached until it reaches the malignant cell.
In laboratory tests, the gold/iron-oxide nanoparticle successfully targeted cancer cells and released the anti-cancer drugs into the malignant cells, killing the cells in up to 80% of cases. The researchers now intend to use the nanoparticle system in laboratory tests with animals. They also plan to create twin nanoparticles that can release drugs via remote-controlled magnetic heating.
Elsewhere, a team at Purdue University (West Lafayette, IN) has come up with a similar approach to the Brown team: in this case combining gold nanorods with magnetic iron-oxide particles. The magnetic particles can be traced via MRI, while the nanorods are luminescent and can be traced through optical microscopy. While MRI is less precise than optical luminescence in tracking the probes, it has the advantage of being able to track them deeper in tissue (Angew. Chem. Int. Ed. 48 2759).
The Purdue probes also contain the antibody Herceptin, which locates and attaches to protein markers on the surface of cancer cells. The team has tested the probes in cultured cancer cells and now plans experiments in mice models to determine the dose and stability of the probes.
"When the cancer cell expresses a protein marker that is complementary to Herceptin, then it binds to that marker," explained Joseph Irudayaraj, a Purdue associate professor of agricultural and biological engineering. "The probe could carry drugs to target and treat, as well as reveal cancer cells. We are advancing the technology to add other drugs that can be delivered by the probes."
About the author
Tami Freeman is Editor of medicalphysicsweb.