Life Extension Magazine

Life Extension Magazine December 2007

Report

Advances in Nanomedicine

By Christopher Windham

The Future: Nanorobots and Nanoprobes

One of the pioneers in the field of nanotechnology is Ralph Merkle. Dr. Merkle has advocated for the engineering of computer-controlled tools that are smaller than cells, and can be built with the precision of drug molecules. In the paper, Nanotechnology and Medicine, Merkle argues that such tools will enable doctors to intervene at the cellular and molecular level, to remove barriers to the circulatory system, kill cancer cells, or control subcellular organelles.7

“Molecular machines will be able to heal and cure,” says Merkle, a computer scientist formerly affiliated with the Georgia Institute of Technology in Atlanta. “With technology, the tools will be very precise and will help us do better with aging and disease.”

The results, Merkle says, will be seen in two phases. In the near future, Dr. Merkle predicts that dendrimers will be able to aid the drug-delivery process. But the more high-profile areas of nanomedicine aren’t likely to occur for many years, until after scientists have learned how to build nanorobots. For example, Freitas has designed nanorobots that could serve as artificial red blood cells, called “respirocytes,” which would carry oxygen through the body, and ultimately to the lungs. In the event of a heart attack, the artificial blood cells would keep the body oxygenated long enough for an individual to seek treatment.

“These artificial blood cells would let you hold your breath for over an hour, and would continue to provide oxygen to your organs even after you fail,” Merkle says. “We are going to be able to build on this in coming decades.”

Other researchers have explored the utility of nanoprobes—that is, designer nanoparticles used for imaging, detecting, and measuring biological changes in cells, tissues, and organs associated with age-related diseases.

The first step, Merkle says, is to create machines capable of building nanoprobes. That feat should be accomplished in 10-20 years, he says. Nanoprobes could be effective in treating certain diseases because they would use only a small amount of radiation to effectively ward off bacterial and viral organisms.

Nanoprobes could also be effective in treating and preventing heart disease, scientists say. This approach would enable nanoprobes to prevent the clogging of arteries by clearing the clots as they start to form. In the future, nanoprobes could be administered to people with histories of heart problems, thus saving lives.

A recent study by researchers at the University of California at Davis found that nanoparticle chemicals can be used to slow the growth of tumors in mice—without damaging the surrounding healthy tissue. The study was published in this year’s March issue of the Journal of Nuclear Medicine.8

Researchers injected trillions of nanoprobes into the bloodstream of mice bearing human breast tumors. The probes sought out and latched to receptors on the surface of malignant cells. As a result, the tumor growth rate slowed in the treated animals in a response that correlated closely with the heat dose. The researchers did not see evidence of toxicity related to the nanoprobe injection. By combining nanotechnology, focused nanoprobe therapy, and quantitative molecular-imaging techniques, the scientists say they may have developed a safer treatment technique for breast and other cancers. The researchers, led by Sally DeNardo, professor of internal medicine and radiology at UC Davis, will now begin exploring testing in human subjects.8

Another new study is also edging researchers closer to nanomedicine reality. Australian biotechnology firm EnGeneIC said it has created tiny nano-cells that bind to antibodies, which then target and latch on to cancer cells in the blood. With this approach, scientists are able to use doses thousands of times lower than typical chemotherapy. EnGeneIC wrote on its finding in this year’s May issue of Cancer Cell.9 The firm said the bacterially derived nano-cell, called EnGeneIC delivery vehicle, was safe in animal trials and resulted in significant cancer regression. With regulatory approval, the company says it plans to begin human trials soon.

As some scientists explore how not to harm healthy tissue when treating diseases, others are examining ways to repair already damaged tissue. One approach developed by researchers at Northwestern University uses nanotechnology to develop bone-like material that could be used for repairing bone fractures or treating patients with bone cancer.

The scientists have created designer molecules that can recreate the natural bone structure at the nanoscale level, including collagen nanofibers, according to a study published in the prestigious journal Science in 2001.10 Once the synthetic nanofibers form, they make a gel which could be used in bone fractures or as scaffolds to grow other tissues. The nanofiber gel would help patch the fracture by encouraging the attachment of natural bone cells. The gel also could be used to improve hip and other joint replacements.

Nanotechnolgy is also being used to improve medicine’s diagnostic tools. Scientists at Ohio State University found that nano-sized particles injected into mice can improve ultrasound results. Scientists had previously thought such particles were too small to be imaged by ultrasound waves. Researchers injected a solution of silica nanoparticles into the tail vein of each mouse. They then took ultrasound images of the animals’ livers every five minutes for 90 minutes after the injection, finding that the nanoparticles had accumulated in the animals’ livers. The scientists hypothesized that the study, which was published last year in the journal Physics in Medicine and Biology, could lead to the day when nanotechnology can alert a physician to the early stages of cancer or heart disease.11

Understanding the Scale of Nanotechnology

Nanotechnology deals with materials that are extremely small. One nanometer (nm) is one-billionth of one meter—far too small to be seen with a conventional microscope. A single human hair is about 80,000 nm in width.

To understand the scale involved, here are estimated sizes of various materials used in nanotechnology:12

  • Nanoparticles: 1-100 nm

  • Fullerene: 1 nm

  • Quantum dot: 8 nm

  • Dendrimer: 10 nm

By comparison, structures and materials that occur in nature are typically of the following sizes:

  • Atom: 0.1 nm

  • DNA (width): 2 nm

  • Protein: 5–50 nm

  • Virus: 75–100 nm

  • Materials

  • internalized

  • by cells: <100 nm

  • Bacteria: 1,000–10,000 nm

  • White blood cell: 10,000 nm

Materials used in nanotechnology are comparable in size to biological structures.

A quantum dot is about the same size as a small protein (<10 nm), while drug-carrying nanostructures may approximate the size of some viruses (<100 nm).

A Promising Beginning

Despite the advancements in the laboratory setting, scientists bemoan the lack of long-term funding for their nanomedicine projects. Thus far, the federal government, through its NIH grants, has been one of the primary funders of the nanomedicine research. Biotech firms and other technology- focused companies have also provided support. But the multi-billion dollar research budgets of big pharmaceutical companies have been missing. Why? Research and development executives are hesitant to spend heavily on research where the practical benefits appear so far away.

“They want to know what’s the pay off,” says Dr. Merkle. “There’s a lot of inherent [financial] interest in the near-term capabilities. But there is less funding for the long-term capabilities.”

Yet scientists are forging ahead, believing that nanotechnology will eventually transform medicine, thus saving and prolonging lives.

“This is just the beginning,” Dr. Merkle says. “But we’re off to a great start.”

If you have any questions on the scientific content of this article, please call a Life Extension Health Advisor at 1-800-226-2370.

Applications of Nanotechnology Nanotechnology may have many important applications in the field of medicine, including:

Implantable Devices

Assessment and Treatment Devices

Implantable Sensors

Implantable Medical Devices

Sensory Devices

Retina Implants

Cochlear Implants

Surgical Aids

Operating Tools

Smart Instruments

Surgical Robots

Diagnostic Tools

Genetic Testing

Ultra-sensitive Labeling and Detection Technologies

High Throughput Arrays and Multiple Analyses

Imaging Tests

Nanoparticle Labels

Imaging Devices

Biopharmaceutics

Drug Delivery

Drug Encapsulations

Functional Drug Carriers

Drug Discovery

Implantable Materials

Tissue Repair and Replacement

Implant Coatings

Tissue Regeneration Scaffolds

Structural Implant Materials

Bone Repair

Bioresorbable Materials

Smart Materials

References

1. Available at: http://www.nanomedicine.com. Accessed September 25, 2007.

2. Available at: http://nihroadmap.nih.gov/overview.asp. Accessed September 25, 2007.

3. Available at: http://209.85.165.104/search?q=cache:uw-FMjaoqUUJ:

www.freedomtocare.org/page316.htm+gilead+sciences+anti-cancer+and+nano&hl=en&ct=clnk&cd=11&gl=us. Accessed September 25, 2007.

4. Available at: http://www.zyvex.com/nanotech/feynman.html. Accessed September 25, 2007.

5. Drexler KE. Engines of Creation: The Coming Era of Nanotechnology. New York, NY: Anchor;1987.

6. O’Neal DP, Hirsch LR, Halas NJ, Payne JD, West JL. Photo-thermal tumor ablation in mice using near infrared-absorbing nanoparticles. Cancer Lett. 2004 Jun 25;209(2):171-6.

7. Available at: http://www.zyvex.com/nanotech/nanotechAndMedicine.html. Accessed September 25, 2007.

8. DeNardo SJ, DeNardo GL, Natarajan A, et al. Thermal dosimetry predictive of efficacy of 111In-ChL6 nanoparticle AMF—induced thermoablative therapy for human breast cancer in mice. J Nucl Med. 2007 Mar;48(3):437-44.

9. MacDiarmid JA, Mugridge NB, Weiss JC, et al. Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics. Cancer Cell. 2007 May;11(5):431-45.

10. Hartgerink JD, Beniash E, Stupp SI. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science. 2001 Nov 23;294(5547):1684-8.

11. Liu J, Levine AL, Mattoon JS, et al. Nanoparticles as image enhancing agents for ultrasonography. Phys Med Biol. 2006 May 7;51(9):2179-89.

12. Available at: http://nanomednet.org/reports/Nanomedicine%20taxonomy.pdf. Accessed October 2, 2007.