Some describe nanotechnology as the new industrial revolution. It presents new opportunities for diagnosis and testing as well as treatment. The technology uses miniaturized disease markers—nanoparticles—that can not only deliver drugs but also cause human cells to create their own medicine. Nanotechnology deals with objects less than about 1,000 nanometers (a nanometer is one-billionth of a meter).

Broadly defined, nanotechnology refers to a field of applied science and technology that involves the control of matter on the atomic and molecular scale—normally one to 100 nanometers—and the fabrication of devices within that size range. It draws from such fields as applied physics, materials science, interface and colloid science, device physics, supramolecular chemistry, chemical engineering, mechanical engineering, and electrical engineering. There’s been widespread speculation as to what may result from these lines of research and some concern about the environmental consequences of some of its applications.

There have been commercial applications of nanotechnology using colloidal nanoparticles in bulk form in such areas as suntan lotions, cosmetics, protective coatings, drug delivery, and stain-resistant clothing.

A significant medical value of nanotechnology is that it can extend the limits of current molecular diagnostics and enable point-of-care diagnosis as well as the development of personalized medicine. Nanotechnology can be seen as an extension of existing sciences into the nanoscale, or as a recasting of existing sciences using a newer, more modern term.

According to the National Cancer Institute, nanotechnology will change the very foundations of cancer diagnosis, treatment, and prevention.

In the treatment area, nanotechnology can carry small amounts of a drug to a specific site where it is needed or can enter a cell and trigger mechanisms that cause the cell to become a drug factory to supply the needed therapy. And some envision a general nanoparticle used as a drug-delivery vessel that could enter a person’s bloodstream and go to a target, bringing small doses of drugs already approved as therapy.

Nanobiotechnologies that are clinically relevant have the potential to be incorporated in clinical laboratory diagnosis. Nanotechnologies enable diagnosis at the single-cell and molecular level, and some of these can be incorporated in the current molecular diagnostics such as biochips. Nanoparticles, such as gold nanoparticles and quantum dots, are the most widely used, but various other nanotechnologies for manipulation at nanoscale as well as nanobiosensors exist.

Nanotechnology-Based Diagnostics for Cancer

Although the potential diagnostic applications are unlimited, the most important current applications are foreseen in the areas of biomarker research, cancer diagnosis, and detection of infectious microorganisms.

Utlizing nanotechnology to identify rare cells in the blood that indicate disease.

Carrie Mulherin, a consultant, is the former vice president of marketing for Immunicon Corp, Huntingdon Valley, Pa, a cancer diagnostic company that uses nanomagnetic particles to isolate circulating tumor cells (CTCs) from blood. She notes that nanoparticles are extremely tiny, even in comparison to cells—some as small as 10 to 50 nanometers. And she says that nanotechnology is probably not yet used extensively outside research and treatment. But even though labs are a small part of the nanotechnology boom, it still has lab applications.

Immunicon’s lab testing application, the CellSearch™ Circulating Tumor Cell Kit, utilizes nanotechnology to identify rare cells in blood associated with diseases. The presence of CTCs in the peripheral blood, as detected by the CellSearch Kit, is associated with decreased progression-free survival (the length of time during and after treatment in which a patient remains alive with a disease or condition, but the disease or condition is not getting worse) and decreased overall survival in patients treated for metastatic breast, colorectal, and prostate cancers.

The test is designed to be used as an aid in the monitoring of patients with metastatic breast, colorectal, or prostate cancer. Serial testing for CTCs should be used in conjunction with other clinical methods for monitoring breast cancer. A CTC count above the threshold (three or five CTCs per 7.5 mL of blood) at any time during the course of the disease is predictive of shorter progression-free survival and overall survival.

In December 2006, the FDA cleared expanded claims for the CellSearch Kit in metastatic breast cancer, in November 2007 for colorectal cancer, and in February 2008 for prostate cancer. The original data in breast cancer demonstrated that more than five CTCs per 7.5 mL of blood drawn at the baseline and at first follow-up after initiation of a new line of therapy predict shorter progression-free survival and overall survival. The new data in the submission extended the median follow-up time to approximately 20 months and proved that CTC results are predictive of survival at monthly time points during treatment for metastatic breast cancer.

The differences were statistically significant for patients undergoing chemotherapy as well as those receiving hormonal therapy. In multivariate analyses, CTC levels were strong, independent predictors of poor outcome. Because the CTC results have been proven to be informative at multiple time points, this expanded claim acknowledges the clinical utility of the CellSearch Kit for the oncologist in the management of their metastatic breast cancer patients.

Mulherin explains that nanotechnology is just one component of a reagent. A nanoparticle is coated with antibodies against cancer cells so one blood cell can be isolated. The CellSearch kit and the CellTracks® AutoPrep® System are used together to enrich a tube of blood down to 320 microliters, stain it, and dispense the sample into a cartridge, which is scanned by the CellTracks Analyzer II. Normally, imaging studies such as CT scans require long time intervals running up to several months to determine if a therapy is effective. While waiting for those results, cancer patients must endure therapies that can make them sick. The CellSearch test is a blood test and can indicate the effectiveness of therapy in as little as 3 to 4 weeks, and physicians can adjust treatment accordingly. The method is FDA-cleared for breast, colorectal, and prostate cancer testing.

“I think it’s revolutionary,” Mulherin says. “Monitoring these days with scans is not ideal. Currently, two measurements have to be done on tumors, and that can take 3 months. With CellSearch, the 3- to 4-week time frame is great for both patients and doctors.”

Nanosphere: Applying Nanotechnology to Pharmacogenetics

Immunicon’s CellSearch™ Circulating Tumor Cell Kit.

Michael McGarrity is chief marketing officer for Nanosphere, Northbrook, Ill, a nanotechnology-based molecular diagnostics company that also is applying the technology for lab usage, specifically for decentralized labs. It recently received FDA clearance for its Verigene® System.

Nanosphere was formed at the Northwestern University Nanotechnology Center directed by Chad Mirkin, who sits on the Nanosphere board. The technology has been developed from the lab bench to a commercially cleared instrument for IVD use in the United States and CE Mark in Europe.

Nanosphere’s Verigene System is a benchtop molecular diagnostics workstation that utilizes patented gold nanoparticle technology to detect nucleic acid and protein targets of interest for a variety of applications. McGarrity says the system is easy to use and cost-effective, and will help hospital-based laboratories by providing complex testing normally reserved for the centralized labs and more timely results, improving disease diagnosis and patient care. “We’re bringing the technology down to the size and scale of the biology,” he says.

A significant advantage of the technology as applied is in its capability to multiplex, or detect multiple nucleic acid targets in a single cartridge. In addition, applied to protein targets, the technology significantly improves sensitivity, allowing for earlier detection of disease. This will advance the viability and clinical utility of both new and existing disease biomarkers.

“We have made the turn from a commercial standpoint,” McGarrity notes. “We received FDA clearance in October. Initial tests were cleared for detection of genetic mutations associated with hypercoagulation disorders and pharmacogenetic application for the widely used anticoagulant Warfarin. The former being one of the most commonly used molecular diagnostics tests offered in the local setting, and the latter addressing the FDA recommended genotyping for patients being prescribed the anticoagulant Warfarin.

“A compelling benefit of the ease of use and turnaround time for Warfarin in particular allows for a result in a 2-hour on-demand format allowing for rapid application of the genetic information to improve patient care and reduce risk associated with adverse reactions,” he continues.

From the outset, the Verigene System was designed to make molecular diagnostic testing simple, accessible, and flexible for users, but still provide the high sensitivity, accuracy, and rapid multiplex target detection required by these applications.

Nanosphere’s Verigene® System.

At the core of each Verigene System are two laboratory instruments—the Verigene Reader and the Verigene Processor—and singleuse laboratory consumables— the Verigene Test Cartridges. The FDA has cleared them for in vitro diagnostic use with specific Verigene Tests. Additional tests for cystic fibrosis carrier screening, respiratory influenza, and hereditary hemochromotosis are in development.

Nanosphere also is in development on a Cardiac Troponin assay with improved diagnostic sensitivity on which the company presented data in a symposium at the recent American College of Cardiology. This application has the potential to significantly improve the risk stratification of cardiac patients. Additional applications for cancer diagnostics are under way at both Nanosphere and Northwestern.

In 2004, the National Cancer Institute unveiled a plan to eliminate death and suffering from cancer by 2015. As part of that effort, the NCI Cancer Nanotechnology Plan provides critical support for the field though extramural projects, intramural programs, and a new Nanotechnology Standardization Laboratory. This facility will develop important standards for nanotechnological constructs and devices that will enable researchers to develop cross-functional platforms that will serve multiple purposes. The laboratory will be a centralized characterization laboratory capable of generating technical data that will assist researchers in choosing which of the many promising nanoscale devices they might want to use for a particular clinical or research application. In addition, this new laboratory will facilitate the development of data to support regulatory sciences for the translation of nanotechnology into clinical applications.

The six major challenge areas of emphasis are:

Prevention and Control of Cancer

  • Developing nanoscale devices that can deliver cancer-prevention agents; and
  • Designing multicomponent anticancer vaccines using nanoscale delivery vehicles.

Early Detection and Proteomics

  • Creating implantable, biofouling-indifferent molecular sensors that can detect cancer-associated biomarkers that can be collected for ex vivo analysis or analyzed in situ, with the results being transmitted via wireless technology to the physician; and
  • Developing “smart” collection platforms for simultaneous mass spectroscopic analysis of multiple cancer-associated markers.

Imaging Diagnostics

  • Designing “smart” injectable, targeted contrast agents that improve the resolution of cancer to the single-cell level; and
  • Engineering nanoscale devices capable of addressing the biological and evolutionary diversity of the multiple cancer cells that make up a tumor within an individual.

Multifunctional Therapeutics

  • Developing nanoscale devices that integrate diagnostic and therapeutic functions; and
  • Creating “smart” therapeutic devices that can control the spatial and temporal release of therapeutic agents while monitoring the effectiveness of these agents.

To keep up to speed on nanotechnology and other emerging technologies, bookmark our website.

Quality-of-Life Enhancement in Cancer Care

  • Designing nanoscale devices that can optimally deliver medications for treating conditions that may arise over time with chronic anticancer therapy, including pain, nausea, loss of appetite, depression, and difficulty breathing.

Interdisciplinary Training

  • Coordinating efforts to provide cross-training in molecular and systems biology to nanotechnology engineers and in nanotechnology to cancer researchers; and
  • Creating new interdisciplinary coursework/degree programs to train a new generation of researchers skilled in both cancer biology and nanotechnology.

What about the environmental concerns expressed by some about nanotechnology? McGarrity says there isn’t enough data to support such concerns. In any case, that focus is on cases when nanoparticles are injected or ingested and on cosmetics and pharmaceuticals, not in diagnostic use, he says.

Editor’s note: Immunicon’s assets were recently acquired by Veridex LLC; current product claims may differ from comments presented.

Gary Tufel is a contributing writer for CLP.