05.05.2014

Gold nanoparticles and cancer treatment

Cancer affects about seven million people worldwide, and that number is projected to grow to 15 million by 2020.
Nanobotmodels present visualization nanoparticle cancer treatment - Nanoparticle cancer treatment: This nanoparticles has the potential to improve upon photothermal tumor ablation for cancer therapy.
Hosoya, et al.'s hydrogel platform consists of bacteriophage, gold nanoparticles, and nano-sized carriers such as liposomes or mesopourous silica particles. The next step was to demonstrate that the HSL-containing hydrogels responded to NIR heating while within a matrix. To determine the heat distribution in the hydrogel from NIR, they used magnetic resonance temperature imaging on the HSL-containing hydrogels on the agarose platform. While these results show that drug release can be controlled using NIR, they still need to test whether the system can target the cancer site.
This work demonstrates a hydrogel platform that does not change the physical or chemical properties of known nanocarrier systems such as heat-sensitive liposomes or mesoporous silica nanoparticles.
Abstract A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Proteins and other therapeutic compounds injected directly into the blood stream tend to be broken down rapidly by the immune system. Self-assembling peptides are characterized by a stable I?-sheet structure and are known to undergo self-assembly into nanofibers that could further form a hydrogel. Using steam to control complex chemistry heralds the next generation of heat sensitive smart gels for medicine.
Some drug regimens, such as those designed to eliminate tumors, are notorious for nasty side effects.
Among the unusual properties of graphene, one of the most exciting and least understood is the additional degree of freedom experienced by electrons.
A team of University of Pennsylvania researchers has developed a computer model that will aid in the design of nanocarriers, microscopic structures used to guide drugs to their targets in the body. IBM scientists have created randomly spiking neurons using phase-change materials to store and process data.
DNA can mediate the assembly of nanoparticles and polymers into multifunctional superstructures and control their interactions with biological systems, potentially allowing for applications in cancer imaging and drug delivery while mitigating the risks of toxicity associated with engineered nanomaterials. Over the past several years, researchers have discovered that nanostructures, built from nanoparticles can be used to deliver drugs directly to a tumor, killing it. The concept was tested in mice, and results thus far indicate that the process worked as planneda€”the team was able to actually see the nanostructures as they appeared in the mouse urine, proving that the mice's systems were able to remove the smaller sized nanostructures from the tumor site and pass them through to the renal system. The researchers report that their technique at this time shows promise, but of course, more work will have to be done to prove that the technique is safe, and that the nanostructures can hold together long enough to do their job.
Abstract The assembly of nanomaterials using DNA can produce complex nanostructures, but the biological applications of these structures remain unexplored.
Nanoscale "cages" made from strands of DNA can encapsulate small-molecule drugs and release them in response to a specific stimulus, McGill University researchers report in a new study. Nanoparticles are typically smaller than several hundred nanometers in size, comparable to large biological molecules such as enzymes, receptors, and antibodies. In this setting, phage particles are able to recognize specific molecules on the tumor cells.
The thermal gradient images confirmed that the centralized heat was produced by the hydrogel via the NIR laser. To do this, Hosoya, et al incorporated a ligand that has a well-established cyclic peptide that binds to CRKL.


They tracked the location and effects of their HSL-containing hydrogel platform in mice that had EF43.fgf-4 mammary carcinoma.
This platform allows for targeting, heat-induced delivery, and is both versatile and reproducible. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release, Proceedings of the National Academy of Sciences (2016). Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo.
Unwanted symptoms are often the result of medicine going where it's not needed and harming healthy cells. In their paper published in the journal Nature Nanotechnology, the team describes a technique they developed where they used DNA strands to tie together small nanostructures creating larger nanostructures, that over timea€”after a tumor had been reduceda€”broke down and left the body.
This is preferential to chemotherapy because it harms only tumor cells, rather than healthy cells throughout the body.
They believe their work will lead to new types of cancer killing agents, but they won't be ready for use in humans for at least five to ten years.
Here, we describe the use of DNA to control the biological delivery and elimination of inorganic nanoparticles by organizing them into colloidal superstructures. Or at least use the specific bonds of DNA molecules to get nanostructures to grow themselves right in the test tube?
With the size of about one hundred to ten thousand times smaller than human cells, these nanoparticles can offer unprecedented interactions with biomolecules both on the surface of and inside the cells, which may revolutionize cancer diagnosis and treatment.The development and optimization of near-infrared-absorbing nanoparticles for use as photothermal cancer therapeutic agents has been ongoing.
One method researchers have used to target cancer cells is to create hydrogels made of filamentous bacteriophage (phage) and gold nanoparticles.
Additionally, they demonstrate that their platform is generalizable to different targets and chemotherapeutics. They found that the HSL-containing hydrogel responded to NIR heating and as laser power increased, the temperature of the hydrogel increased. They used gadolinium-encapsulated HSL-containing hydrogels to confirm that drug release occurred at the location of laser beam. Optical fluorescence imaging studies showed the tumor was visible in mice treated with the targeted hydrogel system compared to controls. With additional studies, this system could be a general, robust method for targeted drug delivery.
In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. The down side is that the nanostructures are made of materials that are considered toxic if they build up in the body and worse, are a little too big for the body to break down and get rid of. The individual nanoparticles serve as building blocks, whose size, surface chemistry and assembly architecture dictate the overall superstructure design. Nanoparticles (35-55nm) provide higher absorption (98% absorption and 2% scattering for gold nanoshells) as well as potentially better tumor penetration. Using calcein, a fluorescently active molecule, they determined that HSL released calcein upon reaching 40oC, as predicted. They then determined whether NIR heating would trigger the release of doxorubicin (dox), a chemotherapeutic.
Using rhodamine-labeled HSL-containing hydrogels, they demonstrated that the phage targeted the carcinoma cells, confirming that it still maintains its binding properties even when incorporated into the nanoplatform. Analysis of the tumors after 24 h revealed that gold nanoparticles, targeted phage, and HSLs were located within the tumor.


Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. These superstructures interact with cells and tissues as a function of their design, but subsequently degrade into building blocks that can escape biological sequestration. The ability to ablate tumor cells in vitro and efficacy for photothermal cancer therapy clinically tested, and an in vivo model shows significantly increased long-term, tumor-free survival. When the HSL was left at a constant temperature (42oC), it released all of the calcein within 10 minutes.
Additional studies to see if their system could then release a chemotherapeutic using NIR at the tumor site also proved successful. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer.
To get around this problem, the researchers took a very unique approach, they used DNA strands to tie small nanostructures together, creating a large enough structure to transport tumor killing drugs.
We demonstrate that this strategy reduces nanoparticle retention by macrophages and improves their in vivo tumour accumulation and whole-body elimination. This nanoparticles has the potential to improve upon photothermal tumor ablation for cancer therapy.One heat therapy to destroy cancer tumors using nanoparticles is called AuroShell?. The authors observed reduced tumor growth in mice with HSL-containing hydrogels with dox, and confirmed their results using mathematical modeling.
Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. But because they are tied together with DNA, they become untied as the body breaks down the DNA strands. Superstructures can be further functionalized to carry and protect imaging or therapeutic agents against enzymatic degradation.
The AuroShell? nanoparticles circulate through a patients bloodstream, exiting where the blood vessels are leaking at the site of cancer tumors. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. Once loosed, the nanostructures revert back to groups of smaller structures which the body can process and get rid of.
These results suggest a different strategy to engineer nanostructure interactions with biological systems and highlight new directions in the design of biodegradable and multifunctional nanomedicine.
Once the nanoparticles accumulate at the tumor the AuroShell? nanoparticles are used to concentrate the heat from infrared light to destroy cancer cells with minimal damage to surrounding healthy cells. Nanospectra Biosciences has developed such a treatment using AuroShell? that has been approved for a pilot trial with human patients.Gold nanoparticles can absorb different frequencies of light, depending on their shape. Rod-shaped particles absorb light at near-infrared frequency; this light heats the rods but passes harmlessly through human tissue. Sphere-shaped nanoparticles absorb laser radiation and passes harmlessly through human tissue too.Nanobotmodels Company provides visual illustration of nanoparticle cancer treatment.
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