Nanotechnology Used to Modify Chemotherapy Drug That May Improve Cancer Treatment
An international collaboration of scientists have developed a larger cisplatin molecule that can be delivered effectively to a tumor but cannot be absorbed by the kidney.
A powerful chemotherapy drug has been modified using nanotechnology to make it less toxic to the kidneys. It is hoped that owing to the reduced toxicity clinicians may be able to use the new drug at higher doses in cancer patients, making it more effective at combating tumors.
The first-line chemotherapy drug cisplatin is popular owing to it being relatively inexpensive and effective against a number of cancers; however, its use is limited owing to nephrotoxicity.
The drug works by delivering toxic platinum atoms to tumor sites and is particularly effective owing to the ease with which platinum is released. The problem lies in the fact that deposited platinum atoms are also toxic to the kidneys and accumulation in the kidney is undesirable.
Other chemotherapy drugs are used that do not give up their platinum loads as readily. This results in fewer toxic side effects but their effectiveness against tumors is also reduced.
An international collaboration of scientists, including Shiladitya Sengupta (Brigham and Women‘s Hospital, MA, USA) have recently developed a larger cisplatin molecule that can be delivered effectively to a tumor but cannot be absorbed by the kidney.
The larger drug molecule was developed by binding many cisplatin molecules with a specially designed polymer that encouraged the whole molecule to form a ball shape 100 nm in size. Particles more than 5 nm in size cannot pass into the kidney, so toxic build up of cisplatin in the kidney would be almost completed reduced.
“It showed absolutely minimal toxicity to the kidney,” Sengupta explained.
The new compound has been found to be effective in delaying tumor growth in breast and lung cancers, as well as outperforming standard cisplatin in an ovarian cancer model. The research has yet to reach human trials and lengthy testing will be required before the new molecule is ready for patient care.
The authors of the recent Proceedings of the National Academy of Sciences paper conclude that “given the universal need for a better platinate, we anticipate this coupling of nanotechnology and structure–activity relationship to rationally reengineer cisplatin could have a major impact globally in the clinical treatment of cancer.”
Source: Paraskar AS, Soni S, Chin KT et al.: Harnessing structure-activity relationship to engineer a cisplatin nanoparticle for enhanced antitumor efficacy. Proc. Natl Acad. Sci. USA 107(28), 12435–12440 (2010).
Nanoparticles Combined with Adult Stem Cells May Eliminate Plaque Build-Up in Arteries
A recent study, reported at the American Heart Association‘s Basic Cardiovascular Sciences 2010 Scientific Sessions, suggests that a nanotechnology technique could be used to rid blocked arteries of plaque build-up. The new technique shows promise for treating atherosclerosis. Since the technique actually destroys plaque it is an advance on current treatments, which restore blood flow by widening arteries and pushing plaque build-up aside.
The study, funded by private investors and the Research Center of Regenerative Medicine (Ural State Medical Academy, Yekaterinburg, Russia) used pig hearts to test the nanotechnology treatment. In total 19 pigs received silica-gold nanoshells, while the 18‑strong control group received only saline solution.
The hearts were infused with nanoparticles via three different procedures. Nanoparticles were delivered either intracellularly combined with adult stem cells; via a bioengineered patch containing adult stem cells, attached to the artery by minimally invasive surgery; or through an infusion of gas-filled, protein-coated microbubbles containing no stem cells.
Once delivered the nanoparticles were heated by laser light. This part of the procedure successfully burned away arterial plaque; the process was found to be most effective at eliminating plaque when the nanoparticles were combined with adult stem cells.
The nanoparticles groups showed an immediate decrease in plaque volume (an average of 28.9% across the three delivery groups) and after 6 months the volume had declined still further (56.8% on average). Conversely, the control group showed an increase in plaque volume over 6 months.
Both of the groups that received the nanoparticle stem cell combination also showed signs of new blood vessel growth and restoration of artery function.
“Nanoburning in combination with stem cell treatment promises demolition of plaque and functional restoration of the vessel wall,” explained lead author Alexandr Kharlamov (Department of Internal Medicine and Research Center of Regenerative Medicine, Ural State Medical Academy, Yekaterinburg, Russia).
“This unique approach holds promise for use in humans for acute care and urgent restoration of blood flow,” Kharlamov enthused.
Source: American Heart Association (21 July, 2010). Nanoparticles plus adult stem cells demolish plaque, study finds. Science Daily: www.sciencedaily.com/releases/2010/07/100719215830.htm
Nanofilm Developed to Rejuvenate Dental Tissue Could Advance Root Canal Treatment
A recent development in nanomedicine could help revitalize damaged teeth
Root canal procedures are used to remove the damaged, painful tissue inside a diseased or injured tooth. Although the procedure is generally successful, it leaves the patients with a dead tooth. A preferable treatment has been sought for a long time and now it seems that nanotechnology may have provided the answer.
A team of scientists led by Nadia Benkirane-Jessel (Institut National de la Santé et de la Recherche Médicale, Strasbourg, France) have developed a multilayered, nanosized film that could help to regenerate dental pulp. It is hoped that the tiny film, which measures only 1/50,000th the thickness of a human hair, could be used to regenerate tissue and replace the disease pulp that is removed during a root canal procedure.
The nanofilm contains alphα-MSH combined with an anti-inflammatory polymer – poly-L-glutamic acid (PGA-α-MSH). The study aimed to define the effects of PGA-α-MSH on fibroblasts, the main type of cell found in dental pulp. PGA-α-MSH was found to have to potential to promote human pulp fibroblast adhesion and cell proliferation.
By using PGA-α-MSH the team were able not only to increase the viability of cells, but also the cell proliferation, providing a revolutionary alternative to pulp removal.
The study, recently published in ACS Nano, is the first of its kind to use nanostructured multilayered films containing α-MSH as the active biomaterial for dental tissue regeneration.
Source: Fioretti F, Mendoza-Palomares C, Helms M et al.: Nanostructured assemblies for dental application. ACS Nano 4(6), 3277 (2010).
Study Suggests Nanoparticles May Assist Early Detection of Melanoma
Gold nanoparticles could act as an in vivo contrast agent for sensitive and selective imaging of early-stage melanoma
A recent study has revealed that gold nanoparticles could be used to improve imaging and detection of melanoma. The research, reported in ACS Nano, was performed by a group of scientists based at the University of Washington, in St Louis, USA. The research, led by Lihong Wang and Younan Xia, could help to improve early detection of melanoma and therefore improve patient survival rates.
The scientists developed novel contrast agents by attaching a peptide that is known to target skin cancer cells to a hollow gold nanocage. When these nanocages were injected into mice, they targeted skin cancer cells and gave a threefold improvement in images of the melanoma obtained, when compared with nanoparticles without the peptide moiety.
Melanoma is the most serious form of skin cancer, and thick melanomas are associated with a high risk of distant metastases. Therefore, early diagnosis of melanoma is a fundamental step in improving patient survival rates. The 5‑year survival rate for melanoma detected at an early stage is as high as 98%; however, when detection occurs at a more advanced stage the survival rate can reduce to as little as 15%.
Current detection techniques are limited by shallow penetration depths and poor resolution. The current techniques also cannot effectively resolve the margins of tumours; surgical removal of the entire primary tumour is significantly improved when the margins of the melanoma are accurately imaged.
A new technique, termed photoacoustic tomography, is a hybrid imaging technique that allows greater image depths and is based on the photoacoustic effect. Photoacoustic imaging works by absorption of light by tissues, in this case the melanoma, this causes a slight heating effect and therefore thermoelastic expansion. If the light is pulsed, the tissue undergoes expansion and contraction, generating an acoustic signal.
“We detect the sound signal outside the tissue, and from there on it‘s a mathematical problem,” comments Wang. “We use a computer to reconstruct an image.”
Due to the photoacoustic effect this method allows greater depth of penetration and can be used to observe much deeper structures.
“We‘re essentially listening to a structure instead of looking at it,” notes Wang.
The technique allows greater penetration and higher resolution; however, imaging is still a challenge without the use of contrast agents.
Combination of the melanoma targeted gold nanocages and photoacoustic tomography could overcome the current limitations of melanoma detection, allowing early detection of tumours, at higher resolution and with greater specificity, therefore improving patient survival rates.
Source: Younan Xia, Lihong V, Wang et al.: In vivo molecular photoacoustic tomography of melanomas targeted by bioconjugated gold nanocages. ACS Nano 4(8), 4559–4564 (2010).