Nanodiagnostics, Targeted Drug Delivery Systems and Nanotechnology Enabled Regenerative Medicine For Fighting Disease
azonano.com - August 23, 2006
Background
The ageing population, the high expectations for better quality of life and the changing lifestyle of European society call for improved, more efficient and affordable health care.
Nanotechnology can offer impressive resolutions, when applied to medical challenges like cancer, diabetes, Parkinson's or Alzheimer's disease, cardiovascular problems, inflammatory or infectious diseases.
Experts of the highest level from industry, research centers and academia convened to prepare the present vision regarding future research priorities in NanoMedicine. A key conclusion was the recommendation to set up a European Technology Platform on NanoMedicine designed to strengthen Europe's competitive position and improve the quality of life and health care of its citizens. This article has been extracted from the vision paper “European Technology Platform on NanoMedicine - Nanotechnology for Health” produced by the European Commission.
Introduction
Artificial nanostructures, such as nanoparticles and nanodevices, being of the same size as biological entities, can readily interact with biomolecules on both the cell surface and within the cell.
Nanomedical developments range from nanoparticles for molecular diagnostics, imaging and therapy to integrated medical nanosystems, which may perform complex repair actions at the cellular level inside the body in the future.
For the purpose of this Vision Paper, NanoMedicine encompasses the three interrelated themes of:
· nanodiagnostics including imaging
· targeted drug delivery and controlled release
· regenerative medicine.
Nanodiagnostics
In nanodiagnostics, the ultimate goal is to identify disease at the earliest stage possible, ideally at the level of a single cell. To achieve this goal, research and development activities in nanotechnology need to be undertaken to improve the effectiveness of invivo and in-vitro diagnostics. Nanotechnology can offer diagnostic tools of better sensitivity, specificity and reliability. It also offers the possibility to take different measurements in parallel or to integrate several analytical steps from sample preparation to detection into a single miniaturized device. Such a device could, thanks to nanotechnology, contain enough hard wired intelligence and robustness to be used by the patient and deliver a multitude of data to the practitioner. Furthermore, the use of nanoelectronics will improve the sensitivity of sensors based on already established methods.
Improvements of microscopic and spectroscopic techniques towards ultra-high spatial resolution, molecular resolution and ultra-high sensitivity will provide a better understanding of the cell’s complex “machinery” in basic research. The resulting progress should pave the way to more innovative and powerful in-vivo diagnostics tools. In general terms nanotechnology will have great impact on the methodologies available for both disease and drug discovery and consequently impact on the scope and throughput of pharmaceutical developments.
Advancement in in-vivo diagnostics will also rely on molecular imaging and on minimally invasive, implantable devices. In molecular imaging, the goal is to create highly sensitive, highly reliable detection agents that can also deliver and monitor therapy. This is the “find, fight and follow” concept of early diagnosis, therapy and therapy control, sometimes also known as theranostics. The tissue of interest is firstly imaged, using target-specific contrast nanostructures.
Then, the targeting nanostructures, combined with a pharmacologically active agent, can be used for therapy. Finally, monitoring of the results of this therapy over time is possible by sequential imaging.
Earlier and more reliable disease detection will be achieved by using better tracers and contrast agents in combination with better detection systems - progress in which is expected to come through combining existing imaging techniques.
Targeted Drug Delivery Systems
The long-term objective of drug delivery systems is the ability to target selected cells and/or receptors within the body. At present, the development of new drug delivery techniques is driven by the need on the one hand to more effectively target drugs to the site of disease, to increase patient acceptability and reduce healthcare costs; and on the other hand, to identify novel ways to deliver new classes of pharmaceuticals that cannot be effectively delivered by conventional means. Nanotechnology is critical in reaching these goals. Already now nanoparticle formulations make use of the fact that an enlarged surface/volume ratio results in enhanced activity. Nanoparticles are also useful as drug carriers for the effective transport of poorly soluble therapeutics. When a drug is suitably encapsulated, in nanoparticulate form, it can be delivered to the appropriate site, released in a controlled way and protected from undergoing premature degradation.
This results in higher efficacy and dramatically minimises undesirable side effects. Such nanoparticulate delivery systems can be used to more effectively treat cancer and a wide range of other diseases, which call for drugs of high potency.
Drug-delivering microchip technology, resulting from the convergence of controlled release and fabrication technologies evolved for the electronics industry, is also benefiting from the application of nanotechnology.
Further miniaturization and the ability to store and release chemicals on demand offer new treatment options in the fight against disease. A future vision is that nanoparticles will carry therapeutic payloads or genetic content into diseased cells, minimising side effects as the nanoparticles will only become active upon reaching their ultimate destination. They may even check for overdosage before becoming active, thus preventing drug-related poisoning. In the past three decades, the number and variety of controlled release systems for drug delivery applications has increased dramatically. Many utilize polymers that have particular physical or chemical characteristics, such as biodegradability, biocompatibility or responsiveness to pH or temperature changes. In spite of many successful examples, the notion of combining polymer science with concepts from structural biology to provide new strategies and opportunities in the design of novel drug delivery systems adapted to today’s demands, has not been fully embraced. In part progress has been slowed by regulatory submissions.
Regenerative Medicine
It is critical for all nanoparticulates that drug safety is considered in parallel with efficacy. The focus of regenerative medicine is to work with the body’s own repair mechanisms to prevent and treat disabling chronic diseases such as diabetes, osteoarthritis, and degenerative disorders of the cardiovascular and central nervous system and to help victims of disabling injuries. Thanks to nanotechnology, a cellular and molecular basis has been established for the development of innovative disease-modifying therapies for in-situ tissue regeneration and repair, requiring only minimally invasive surgery.
Rather than targeting the symptoms or attempting to delay the progress of these diseases, future therapies will be designed to rectify chronic conditions using the body’s own healing mechanisms. To name some examples: facilitating the regeneration of healthy cartilage in an osteoathritic joint, re-establishing a physiological release profile in diabetic pancreatic islets, or promoting self-repair mechanisms in areas of the central nervous system and of the heart.
Nanotechnology can play a pivotal role in the development of cost-effective therapies for in-situ tissue regeneration. This involves not only a deeper understanding of the basic biology of tissue regeneration, but also identifying effective ways to initiate and control the regenerative process. This ‘nanobiomimetic’ strategy depends on three basic elements:
· Intelligent biomaterials
· Bioactive signalling molecules
· Cells
By ‘tailoring’ resorbable polymers at the molecular level for specific cellular responses, nanotechnology can assist in the development of biomimetic, intelligent biomaterials. These biomaterials are designed to react positively to changes in the immediate environment, stimulating specific regenerative events at the molecular level, directing cell proliferation, cell differentiation, and extracellular matrix production and organization. The sequential signalling of bioactive molecules, which triggers regenerative events at the cellular level, is necessary for the fabrication and repair of tissues. Nano-assisted technologies should enable the sequential delivery of proteins, peptides and genes to mimic nature’s signalling cascade. As a result, bioactive materials are produced, which release signalling molecules at controlled rates that in turn activate the cells in contact with the stimuli.
Finally, a major focus of ongoing and future efforts in regenerative medicine will be to effectively exploit the enormous self-repair potential that has been observed in adult stem cells. Nano-assisted technologies will aid in achieving two main objectives – to identify signalling systems, in order to leverage the self-healing potential of endogenous adult stem cells; and to develop efficient targeting systems for stem cell therapies. Of huge impact would also be the ability to implant cell-free, intelligent bioactive materials that would effectively provide signalling to stimulate the self-healing potential of the patient’s own stem cells.
Source: European Commission |
