Nanomedicine: important new concepts for otolaryngology.

Traditionally, otolaryngologists have embraced new technology and applied it quickly to enhance patient care. The operating microscope, superior surgical instrumentation, advanced operative laryngoscopes, flexible endoscopes, sinus endoscopes, strobovide-olaryngoscopy, and other advances have been embraced for their ability to improve diagnostic accuracy and surgical precision. Twenty-first-century technology offers even greater possibilities to achieve meticulously precise diagnosis and intervention, and otolaryngology patients are likely to benefit from our involvement in research using the latest modalities. Nanomedicine provides new opportunities that have not been explored widely by otolaryngologists.

A nanometer is one billionth of a meter. Nanomedicine involves diagnosis, treatment, and monitoring at the molecular level. It incorporates nanotechnology and medicine through interdisciplinary collaboration. Past interdisciplinary efforts have been very fruitful in otolaryngology in the evolution of subspecialties such as voice and skull base surgery. The collaboration of nanotechnologists, engineers, cell biologists, physicists, mathematicians, physicians, and others has already resulted in fascinating knowledge, some of which is ready to be applied to otolaryngologic disorders. In the future, nanomedicine offers the potential for us to be able to cure disease and restore structure and function at the cellular level, with little trauma and manageable potential toxicity.

Nanomedicine incorporates platform technology for gene therapy, molecular imaging, drug delivery, and treatment of groups of molecules or even single molecules. It is possible already to study cellular activity in vivo using quantum dot (QD) probes. Nanometer-scale biosensors are helping to identify molecules suitable for new drug development. Nanomedicine also includes diagnostic imaging at the molecular level, development of nanopharmaceuticals, research into protein mimicry, and oncologic drug therapy directed specifically to cancer cells. The cancer therapy applications of nanomedicine are particularly interesting. They include markedly increased ability to monitor for the presence of cancer cells in a patient's blood, as well as techniques for studying genetic aspects of cancer.

Nanotechnologic molecular cell assembly with nanofibers has been notable. This approach has been used to repair central nervous system trauma (including injured brain), as well as traumatic injury to other tissues. There should be interesting research possibilities for applying nanotechnology to some particularly challenging otolaryngologic problems, such as restoration of cochlear hair cells, regeneration of acoustic or vestibular nerve fibers, treatment of tinnitus, and treatment of anosmia, among others.

One fascinating spin-off of this research was reported in 2006. While using a self-assembling peptide to address brain injury, Ellis-Behnke et al noticed that rapid hemostasis was achieved. (1) Further research showed that their self-assembling peptide can establish a nanofiber barrier and achieve complete hemostasis virtually immediately in mammals, stopping bleeding not only in the brain and spinal cord, but even from liver laceration or a divided femoral artery. This rapid, complete hemostasis occurs without cauterization, vasoconstriction, coagulation, or even application of pressure. Its potential use in otolaryngology is particularly exciting. (2,3)

To date, assessing single-molecule properties in living cells has been restricted by either the size of the probe or the photobleaching of the small fluorescent labels. QDs are nanometer-sized, fluorescent probes suitable for advanced biologic imaging. The unique, fluorescent spectral characteristics and photostability of the QDs position them above traditional organic dyes for live-cell, time-resolved imaging applications. This approach involves the use of QD probes specifically targeted to known nuclear markers, to elucidate the cellular dynamics of oxidative stress in living cells. The significance of this research lies in the development of platform technology that will impact nanoscale imaging approaches designed to probe molecular mechanisms in the nucleus of living cells.

Nanotechnology will be very useful for drug delivery and diagnostic approaches. Magnetic nanotechnology is finding wide applications in medicine, (4) most notably in magnetic resonance imaging and magnetic separation. The impedance biosensor is expected to find applications in monitoring cytokines in cancer and bone turnover markers in osteoporosis, and in understanding neural-degenerative diseases.

Nanoscale materials offer unique and powerful opportunities for detection of biologic and chemical species central to many areas of healthcare and the life sciences, ranging from disease diagnosis to the discovery and screening of new drug molecules, providing a high-throughput, real-time parallel detection and rapid screening of libraries of biomolecules. The integrated nanowire sensor array platform opens up substantial opportunities for diagnosis and treatment of complex diseases such as cancer, detection of biologic threats, and fundamental proteomic and biophysical studies.

The development of a cancer-therapy monitoring/diagnostic-platform device is intended to provide near real-time monitoring of patient blood for cancer cells and cell-derived nanoparticulates (such as high-molecular-weight DNA fragments), and also carry out subsequent cancer-related genotyping, gene expression, and immunochemical analysis.

Nanotechnology does not come without some drawbacks, of course. Potential ophthalmologic, skin, pulmonary, and vascular toxicity from nanomaterials has been reported. However, it is likely that further research will quickly establish safe, effective technologies for studying and treating a variety of conditions (otolaryngologic and other) with a degree of precision that has been unimaginable in the past. Otolaryngologists should become familiar with this evolving field and might enjoy perusing an excellent new journal called Nanomedicine: Nanotechnology, Biology and Medicine published by Elsevier, currently in its third year.

References

(1.) Ellis-Behnke RG, Liang YX, Tay DK, et al. Nano hemostat solution: Immediate hemostasis at the nanoscale. Nanomedicine 2006; 2(4):207-15.

(2.) Wei C, Lyubchenko YL, Ghandehari H, et al. New technology and clinical applications of nanomedicine: Highlights of the second annual meeting of the American Academy of Nanomedicine (Part I). Nanomedicine 2006;2(4):253-63.

(3.) Heller M, Wei C. Self-assembly peptide prevents blood loss. Nanomedicine 2006;2(4):216.

(4.) Flynn T, Wei C. The pathway to commercialization for nanomedicine. Nanomedicine 2005; 1 (1):47 -51.

Robert T. Sataloff, MD, DMA 

Editor-in-Chief

EAR, NOSE & THROAT JOURNAL

Chiming Wei, MD, PhD, FACC, FAHA, FAAN 

President

American Academy of Nanomedicine

Editor-in-Chief

NANOMEDICINE: NANOTECHNOLOGY, BIOLOGY AND MEDICINE