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Home > Nanotechnology Columns > UAlbany College of Nanoscale Science and Engineering > Nanotechnology and the baby boom come of age
|J. Andres Melendez
CNSE Professor of Nanobioscience
UAlbany College of Nanoscale Science and Engineering
In 2010 the first baby boomers reached official retirement age and an additional 10,000 join the ranks on a daily basis(1). The influx of these 78 million retirees over the next 20 years will dramatically change the U.S. age profile and put a heavy burden on both the retirement and Medicare system. Nanoscience integrates engineering, physical and life sciences and has led to major advances in diagnostics and therapeutics for many age-associated diseases. Nanotechnology is leading to discoveries that will extend the working lifespan, decrease medical visits and significantly reduce burden on the rapidly depleting social retirement system. Federal, state and private investments in nanotechnology will help keep the baby boom from busting the bank.
September 13th, 2011
Nanotechnology and the baby boom come of age
In 2010 the first baby boomers reached official retirement age and an additional 10,000 join the ranks on a daily basis(1). The influx of these 78 million retirees over the next 20 years will dramatically change the U.S. age profile and put a heavy burden on both the retirement and Medicare system. Nanoscience integrates engineering, physical and life sciences and has led to major advances in diagnostics and therapeutics for many age-associated diseases. Nanotechnology is leading to discoveries that will extend the working lifespan, decrease medical visits and significantly reduce burden on the rapidly depleting social retirement system.
The general aging process is often accompanied with increases in degenerative disease burden. Age-associated degenerative disease include but are not limited to arthritis, atherosclerosis, cancer, dementia, pulmonary disease, periodontal disease, stroke and impaired wound healing. More often than not many of these disease processes are treatable using both pharmacologic and dietary intervention when detected early. The limits to early detection include the low levels of circulating biomarkers for a particular disease and existence of biosensors with the sensitivity to monitor subtle shifts in these disease markers. For these reasons it is clear why biosensor development is at the forefront of the nanomedicine initiative.
A wide array of biological nanoscale sensors have been engineered by nature and include: 1. cell surface receptors that detect circulating hormones, growth factors, inflammatory mediators, pathogens and pathogen-associated molecules; 2. catalytic enzymes that in some instances can sense and remove substrates at near diffusion limiting rates and 3. Nucleic acid repair and synthesis enzymes detect nucleotide lesions, chemical modifications and nucleotide sequences at sub-nanoscale levels. Thus, evolution has engineered sensitive biosensors and nanoscience has been handed the task of developing both their diagnostic and therapeutic potential.
Defects which inhibit or enhance natural biosensor activity are associated with many degenerative disease pathologies. The increased production of the family of proteins responsible for modeling and remodeling the extracellular matrix is commonly linked to disease. Aberrant production of these matrix metalloproteinases (MMPs) is in large part responsible for joint destruction associated with arthritis, the invasive nature of malignant tumors, atherosclerotic plaque rupture, breakdown of the blood brain barrier associated with stroke injury and emphysema induced fibrosis. MMPs display substrate specificity with overlap between family members and it is these substrates that have clear potential for biosensor and therapeutic development. Nanoparticles laden with MMP substrates and linked to drugs or imaging agents have been developed which release their cargo at sites of active proteolysis. This approach has been used to deliver chemically labeled MMP-activated fluorogenic peptides near proteolytically active tumors(2). There exists enormous potential for using these nanoparticles in treating a wide variety of diseases where focal proteolytic matrix destruction underlies disease pathogenesis. This same approach can be linked to sensitive nanobiosensor development. Linking MMP-peptide substrates to nanoparticles may eventually yield highly sensitive nanosensors for this large family of matrix modifying enzymes that drive many degenerative disease processes. The College of Nanoscale Science and Engineering (CNSE) at the University of Albany has developed a unique biological high throughput screening system (HTS) which identifies compounds that restrict age‐related MMP expression. We are now in the position to develop nanoparticles that target release of these agents at sites of disease. This approach offers distinct advantages from the use of broad or specific inhibitors of MMP activity, which target MMP activities that are fundamental to physiologic processes, and have been shown to lack clinical benefit.
The CNSE Nanobioscience constellation is developing diagnostic tools to monitor cellular dysfunction in various disease states. Associated with these pathologies are alterations in cellular oxidant production that modulate the redox‐state of the cell. Increased production of reactive oxygen species (ROS) is also linked to many age associated diseases. The free radical theory of aging ,proposed by Denham Harman, suggests that organismal demise is attributed to lifelong exposure to ROS with the ability to damage a diverse array of biomolecules (3). ROS have emerged as key mediators in regulation of signaling networks by modulating phosphatase activity, kinase cascades and transcription factor binding(4). Thus, ROS serve a dual role, at low concentrations they are secondary signaling molecules that regulate the expression of a wide array of signaling networks, and at high concentrations damage lipids, protein and DNA. To date methods for monitoring oxidant production are fairly non‐specific and do not assess real‐time fluctuations in oxidant status. We have developed many cutting edge tools to monitor oxidant production from cells and in real time. These assays are still fairly labor intensive and require a great deal of both biochemical and molecular expertise. Thus, the study of oxidants is lacking a fairly simple and accurate method for monitoring shifts in redox‐state or oxidant production. CNSE technologies are being applied to the development of nanodevices to assess cellular redox state. Redox‐sensors can be designed to rapidly monitor cellular redox‐fluxes that are propagated by many disease insults. This technology can be applied to wide array of diagnostic devices. Redox‐shifts are linked to heart disease, diabetes, metastatic disease, atherosclerosis, arthritis, pulmonary dysfunction and infection. Biochemical and molecular methodologies to monitor oxidant production are being coupled to test the validity and versatility of a redox‐sensors which have the potential to be used as early diagnostic nanosensors of age-related disease.
CNSE is unique in that it provides the scientific infrastructure for the development of innovative therapeutic and diagnostic technologies to meet the medical demands of the rapidly growing aging population.
1. Szinovacz ME (2011) Introduction: The aging workforce: challenges for societies, employers, and older workers. J Aging Soc Policy 23(2):95-100.
2. Lee S, et al. (2009) Polymeric Nanoparticle-Based Activatable Near-Infrared Nanosensor for Protease Determination In Vivo. Nano Letters 9(12):4412-4416.
3. Harman D (1992) Free radical theory of aging. Mutat.Res. 275(3-6):257-266.
4. Finkel T (2011) Signal transduction by reactive oxygen species. The Journal of Cell Biology 194(1):7-15.