This article takes a broad overview of some of the ways nanotechnology is being applied to medical technologies and assesses the impact that this may have for industry.
What nanotechnology has to offer
In covering such a broad subject as nanotechnology, particularly in the context of medicine and life sciences, it is useful to first define the term. The classical definition of nanotechnology is the “design, characterisation, production and application of structures, devices and systems by controlling shape and size at the nanoscale,” where the nanoscale is defined as “having one or more dimensions of the order of 100 nm or less.” However, in biology, many nanostructures of interest, both engineered and natural, are above 100 nm in size. The classical definition must also be extended to encompass the idea of designing structures that have novel or enhanced properties that can be of benefit medically by virtue of being at the nanoscale.
A following question may be, “Why is small important for healthcare?” It must be recognised here that most biological structures are self-assembled from nano-scale elements and that interaction between cells, cellular components or other biological entities normally involve some interaction at the nanoscale. This has important implications in understanding disease and in diagnosing and treating all types of medical conditions.
A third important element is: Will applying nanotechnology bring benefit to medicine and can it be achieved in a health economics climate where cost containment is a critical factor? In other words, can it deliver better treatments or prognoses at an affordable cost?
Early diagnosis of disease
It is commonly acknowledged that the earlier a disease or condition is diagnosed, the better the prognosis for the patient and the lower the costs generally to the healthcare system, for example, by reducing the need for costly treatments or expensive hospital stays. Furthermore, diagnostics can increasingly assist in determining the likely effectiveness of different therapies and in helping patients monitor their own long-term conditions.
In many ways, diagnostic devices lend themselves to the application of nano-technology. The devices themselves are generally remote from the patient and any utilised nanomaterials that would other-wise require extensive biological safety testing do not come into direct contact with the body, except in the case of biosensing surfaces used in in vivo monitoring and diagnosis. The application of nano-technology can come from the use of these materials, from the ability to engineer at the nanoscale or from the combination of different nanoscale disciplines. Advantages of employing nanotechnology or nanoscale features can include
- the need for small samples such as picolitres of analytes
- much faster analysis times because of greatly reduced diffusion distances, high surface to volume ratios and increased reactivity
- extremely low consumption of reagents
- the possibility of analysing many parameters in parallel as a result of the miniaturisation of components, for example, to form the elements of a lab-on-a-chip system
- compactness allows the creation of desktop or handheld systems using disposable modules or chips, which thereby enables devices to be used at the point of care
- high-throughput analysis
- reduced fabrication costs, which allow mass production of disposable chips
- a safer platform for chemical, radioactive or biological studies because of the integration of functionality, the smaller volumes or masses of materials and biological analytes, and lower stored energies.
Apart from the simple reduction in scale, there are many other useful features that nanotechnology can provide, these include
- nanocontoured surfaces or structures, for example, nanopits, nanobumps, nanogrooves on surfaces or scaffolds to facilitate cell adhesion, non-adhesion, growth or movement, which thereby permit a wide range of biological sensing or binding surfaces; nanowires; nanopores that can be used for deoxyribonucleic acid (DNA) sequencing; or other nanoscale features such as functionalised hydrophilic or hydrophobic surfaces
- Nanoscale actuators, for example, as tiny switches or pumps
- Micro- or nanoscale features capable of mimicking the morphology of natural tissue, cellular or subcellular features to more realistically model in vivo metabolic or physiological conditions or stresses; or that can facilitate important natural cell-to-cell signalling in vitro.
In vivo imaging
Medical imaging is another field that contributes to early stage disease identification and diagnosis, but which is increasingly being used to track and monitor the delivery of therapeutic agents. The use of nanoparticles as novel amplification agents for imaging may offer many advantages. It is now possible to functionalise polymer-coated nanoshells, dendrimers and gold nanospheres to enable specific, site-targeted delivery of agents and drugs such as in chemotherapy. The uptake into tumour cells of nanoparticles is rendered significantly easier because of their inherently small size and by the “leaky” vasculature characteristic of tumours and inflamed tissues. The application of these nanostructured contrast agents should lead to lower dose requirements and significant signal amplification, and may also provide the ability to detect primary tumours at a much earlier stage of their development.
Examples of nanoformulated products for magnetic resonance imaging on the market include Resovist (Schering),1 Feridex (AMAG Pharmaceuticals)2 and Endorem (Guerbet SA),3 which are specifically designed for the diagnosis of liver tumours, and GastroMARK (AMAG Pharmaceuticals)2 for the imaging of abdominal structures. Resovist, for example, consists of superparamagnetic iron oxide (SPIO) nanoparticles coated with carboxydextran, a material that enables the SPIOs to be accumulated in healthy cells of the reticuloendothelial system of the liver. Most malignant liver tumours do not contain these cells and therefore do not take up the iron particles and the application of coated nanoparticles leads to an improved contrast between the tumour (bright) and the surrounding tissue (dark).
Scaffolds for regenerative medicine
Regenerative medicine is widely seen as one of the next revolutions in medical treatment. It draws from tissue science, biology, biochemistry, physics, chemistry, applied engineering and other fields and is characterised by a high level of inter-disciplinarity. The general aim of regenerative medicine is to repair or regenerate damaged tissues and organs in vivo through techniques that stimulate them into healing themselves and thereby avoid the introduction of devices constructed from materials that are alien to the body as replacements. These devices often have a finite life within the challenging environment of the body and can give rise to complications during revision surgery to replace them at the end of their working life. Tissues and organs can also be grown in vitro for subsequent implantation into the body.
Regenerative medicine is considered to have huge potential for developing new treatments for previously untreatable, or difficult to treat, diseases and conditions including diabetes, heart and vascular disease, renal failure, musculoskeletal defects and injuries, osteoporosis, and peripheral nerve and spinal cord injuries. Virtually any disease that results from malfunctioning, damaged or failing tissues could have the potential to be treated through regenerative medicine techniques.
A scaffold is a structured environment that physically supports cell growth as part of a tissue repair or regeneration process. Scaffolds can be active (they may incorporate materials or features that help influence or direct cell growth) or inert (they simply provide a shape and physical substrate for the final tissue construct). Essential requirements for a scaffold to be effective in promoting three-dimensional (3D) cell growth and vascularisation, and which can be improved by incorporating nanoscale features, include
- good biocompatibility
- the ability to degrade into non-toxic components that can be eliminated from the body as the synthetic scaffold is replaced by new extracellular matrix produced by the cells
- the ability to exert an effect at molecular level
- the ability to incorporate cell-specific recognition factors such as adhesive proteins or functional domains in extracellular matrix components that promote cell binding to the scaffold
- the ability to include and sequentially target biomolecules that promote cell growth and differentiation into the desired tissue thereby achieving the reparative process
- the ability to enable diffusion of cell nutrients and cell-produced biomolecules
- the ability to react to external inputs in a controlled and predictive manner where needed
- the ability, where appropriate, to be chemically attracting to endogenous
- the ability to react and adapt to changes in physiological parameters
- structural characteristics, particularly in a 3D scaffold such as a high and interconnected porosity that facilitates the vascularisation and innervation of the new tissue, high surface area for cell population and adhesion, and suitable mechanical integrity and physical properties depending on the type of tissue to be produced.
For example, engineered cartilage will only become fully functional when grown in a matrix that allows physical movement such as compression and decompression during growth of the chondrocytes. In addition, chondrocytes are observed to prefer a fibrous scaffold material to lay down their collagen type 2 matrix. The optimal porosity, pore interconnectivity and chemical and mechanical characteristics of scaffolds will also vary according to cell type and intended engineered tissue type. These characteristics comprise a combination of microscale structure and nanoscale surface and functionalisation features in any given scaffold.
The demographic time bomb
By 2060, it is estimated that the European Union will move from having four people aged between 15 and 64 for every person aged over 65, to a ratio of only two to one. The largest decrease is expected to occur between 2015 and 2035 when current baby-boomer generation will be entering retirement.4 These demographic changes will have a dramatic effect on society and are likely to lead to new clinical challenges in relation to diseases associated with the elderly such as arthritis, osteoporosis and other orthopaedic conditions, neuro-degenerative diseases, deafness and certain forms of blindness. This will be further compounded by a reduction in the proportion of the population in active work, which will put further pressure on funding healthcare systems to address these problems.
Timeline to nanotech benefits
It is likely that some of the contributions and potential benefits that nanotechnology can provide can be realised in the relatively near future. This is especially the case where nanotechnology leads to incremental improvements in the performance of existing classes of product such as diagnostic devices, imaging agents and techniques and implants. In other fields such as regenerative medicine, where new paradigms of treatment are being defined and where uptake by clinical professionals trained in conventional techniques is an unknown quantity, development may need to be actively supported to realise new therapeutic benefits.
Data demonstrates that academic research in regenerative medicine is thriving. Unfortunately, a lack of access to suitable capital, regulatory hurdles and a dearth of clinical evidence on cost-effectiveness may lead to problems with utilisation and reimbursement. This is compounded by a culture in Europe that is sometimes considered to be unsupportive in utilising innovative products and does not provide an attractive environment for the commercialisation of regenerative medicine products.5 It had been suggested that these factors have contributed to hindering the progress that the science has made thus far in terms of bringing new products and treatments to the clinic. Addressing these will be just as important as the development of the underlying technology.
4. Communication from the Commission to the European Parliament, the Council, the European Economic and Social Committee and the Committee of the Regions, Dealing with the impact of an ageing population in the EU (2009 Ageing Report), Commission of the European Communities, Brussels, 29.4.2009 COM (2009) 180 final.
is Manager, Nanomedicine and Life Sciences Institute of Nanotechnology, Suite 5/9 Scion House, Innovation Park, University of Stirling Stirling FK9 4NF, UK, tel. +44 1786 458 020 e-mail: firstname.lastname@example.org
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