Hollow gold nanospheres equipped with a targeting peptide find melanoma cells, penetrate them deeply, and then cook the tumor when bathed with near-infrared light, a research team led by scientists at The University of Texas M. D. Anderson Cancer Center reported in the Feb. 1 issue of Clinical Cancer Research.
"Active targeting of nanoparticles to tumors is the holy grail of therapeutic nanotechnology for cancer. We're getting closer to that goal," said senior author Chun Li, Ph.D., professor in M. D. Anderson's Department of Experimental Diagnostic Imaging. When heated with lasers, the actively targeted hollow gold nanospheres did eight times more damage to melanoma tumors in mice than did the same nanospheres that gathered less directly in the tumors.
Lab and mouse model experiments demonstrated the first in vivo active targeting of gold nanostructures to tumors in conjunction with photothermal ablation - a minimally invasive treatment that uses heat generated through absorption of light to destroy target tissue. Tumors are burned with near-infrared light, which penetrates deeper into tissue than visible or ultraviolet light.
Photothermal ablation is used to treat some cancers by embedding optical fibers inside tumors to deliver near-infrared light. Its efficiency can be greatly improved when a light-absorbing material is applied to the tumor, Li said. Photothermal ablation has been explored for melanoma, but because it also hits healthy tissue, dose duration and volume have been limited.
Lower light dose, great damage
With hollow gold nanospheres inside melanoma cells, photothermal ablation destroyed tumors in mice with a laser light dose that was 12 percent of the dose required when the nanospheres aren't applied, Li and colleagues report. Such a low dose is more likely to spare surrounding tissue.
Injected, untargeted nanoparticles accumulate in tumors because they are so small that they fit through the larger pores of abnormal blood vessels that nourish cancer, Li said. This "passive targeting" delivers a low dose of nanoparticles and concentrates them near the cell's vasculature.
The researchers packaged hollow, spherical gold nanospheres with a peptide - a small compound composed of amino acids - that binds to the melanocortin type 1 receptor, which is overly abundant in melanoma cells. They first treated melanoma cells in culture and later injected both targeted and untargeted nanospheres into mice with melanoma, then applied near-infrared light.
Fluorescent tagging of the targeted nanospheres showed that they were embedded in cultured melanoma cells, while hollow gold nanospheres without the targeting peptide were not. The targeted nanospheres were actively drawn into the cells through the cell membrane.
When the researchers beamed near-infrared light onto treated cultures, most cells with targeted nanospheres died, and almost all of those left were irreparably damaged. Only a small fraction of cells treated with untargeted nanospheres died. Cells treated only with near-infrared light or only with the nanospheres were undamaged.
An 8-fold increase in tumor destruction
In the mouse model, fluorescent tagging showed that the plain hollow gold nanospheres only accumulated near the tumor's blood vessels, while the targeted nanospheres were found throughout the tumor.
"There are many biological barriers to effective use of nanoparticles, with the liver and spleen being the most important," Li said. The body directs foreign particles and defective cells to those organs for destruction.
Most of the targeted nanospheres in the treated mice gathered in the tumor, with smaller amounts found in the liver and spleen. Most of the untargeted nanospheres gathered in the spleen, then in the liver and then the tumor, demonstrating the selectivity and importance of targeting.
In another group of mice, near-infrared light beamed into tumors with targeted nanospheres destroyed 66 percent of the tumors, but only destroyed 7.9 percent of tumors treated with untargeted nanospheres.
The researchers used F-18-labeled glucose to monitor tumor activity by observing how much glucose it metabolized. This action "lights up" the tumor for positron emission tomography (PET) imaging. Tumors treated with targeted shells largely went dark.
"Clinical implications of this approach are not limited to melanoma," Li said. "It's also a proof of principle that receptors common to other cancers can also be targeted by a peptide-guided hollow gold nanosphere. We've also shown that non-invasive PET can monitor early response to treatment."
The targeted nanospheres have a number of advantages, said Jin Zhang, Ph.D., professor in the University of California-Santa Cruz Department of Chemistry and developer of the hollow nanospheres. Their size - small even for nanoparticles at 40-50 nanometers in diameter - and spherical shape allow for greater uptake and cellular penetration. They have strong, but narrow and tunable ability to absorb light across the visible and near-infrared spectrum, making them unique from other metal nanoparticles.
The hollow spheres are pure gold, which has a long history of safe medical use with few side-effects, Li said.
Scott Merville | EurekAlert!
Live probiotics can re-balance the gut microbiome and modify immune system response
20.11.2018 | Symprove
Purdue cancer identity technology makes it easier to find a tumor's 'address'
16.11.2018 | Purdue University
Max Planck researchers revel the nano-structure of molecular trains and the reason for smooth transport in cellular antennas.
Moving around, sensing the extracellular environment, and signaling to other cells are important for a cell to function properly. Responsible for those tasks...
Researchers at the University of New Hampshire have captured a difficult-to-view singular event involving "magnetic reconnection"--the process by which sparse particles and energy around Earth collide producing a quick but mighty explosion--in the Earth's magnetotail, the magnetic environment that trails behind the planet.
Magnetic reconnection has remained a bit of a mystery to scientists. They know it exists and have documented the effects that the energy explosions can...
Biochips have been developed at TU Wien (Vienna), on which tissue can be produced and examined. This allows supplying the tissue with different substances in a very controlled way.
Cultivating human cells in the Petri dish is not a big challenge today. Producing artificial tissue, however, permeated by fine blood vessels, is a much more...
Faster and secure data communication: This is the goal of a new joint project involving physicists from the University of Würzburg. The German Federal Ministry of Education and Research funds the project with 14.8 million euro.
In our digital world data security and secure communication are becoming more and more important. Quantum communication is a promising approach to achieve...
On Saturday, 10 November 2018, the research icebreaker Polarstern will leave its homeport of Bremerhaven, bound for Cape Town, South Africa.
19.11.2018 | Event News
09.11.2018 | Event News
06.11.2018 | Event News
20.11.2018 | Life Sciences
20.11.2018 | Life Sciences
20.11.2018 | Physics and Astronomy