There is a general ambiguity in defining ‘nanotechnology’ which stems from the fact that it is highly interdisciplinary in its construct and is subject to various interpretations. The most commonly-cited interpretation is that used by the US National Nanotechnology Initiative (NNI), which says that “Nanotechnology is the understanding and control of matter at the nanoscale, at dimensions of roughly 1 to 100 nanometers, where unique phenomena enable novel application”.

A more rounded definition without any arbitrary size constraint was proposed by Bawa3, which states that “the design, characterisation, production and application of structures, devices and systems by controlled manipulation of size and shape at the nanoscale (atomic, molecular and macromolecular scale) that produces structures, devices and systems with at least one novel/superior characteristic or property”. Nanotechnology is deeply rooted in physical, chemical and biological sciences for inspiration, design, application and implementation. As a technology it owes its development, commercialisation and rapid rise to the highly-competitive semi-conductor industry of chip manufacturing and allied sectors. Now, this technology has spilled out of it into many and widely varied industries, one of which is nanomedicine.

Nanomedicine is a branch of nanotechnology which has its applications in the field of medicine, diagnostics and pharma and drug delivery. Governments, researchers and the markets across the globe realised its potential and have identified various roadmaps for its development and implementation. Nanobiosciences is a better term than nanomedicine to describe this branch as the term nanobiosciences is ‘all-encompassing’ and also includes applications of nanotechnology for and in basic bioscience research among other non-medical but biological applications.

Roadmaps to development of nanomedicine/nanobiosciences
Many agencies and different governments devised their own roadmaps for the development of nanomedicine. One of the most objective and comprehensive roadmaps for nanomedicine was formulated by European Technology Platform on Nanomedicine (ETP-Nanomedicine)4. ETPNanomedicine is an initiative led by the industry in partnership with the European Commission, composed of experts from both industry and academia. They developed a vision statement identifying nanomedicine for having potential impact on prevention, early and reliable diagnosis and treatment of diseases5. The group also identified priority areas for growth and development in nanomedicine for maximum impact. Plus it dealt with predicting market needs and a product development pipeline to meet the demand while trying to assess possible road-blocks for their commercialisation.

The most commonly identified priority areas are:

1. Diagnostics
Devices are designed with an aim to detect disorder or disease at the earliest possible stage and also, identifying at risk patients early. It involves designing devices for imaging or measuring and characterising a body function. For example, it could be imaging cells or some specific molecule with high spatial accuracy or quantifying a certain molecule electrically. These could be designed to be tetherless, portable point of care (POC) systems4. These could also be made for monitoring therapy. It also involves making platforms and developing protocols for genomic and proteomic-based diagnostics. Field effect transistors of various types, quantum dots for imaging, high throughput immunoassays and live cell imaging make up a few of the common nanotechnology- based development along with devices for genomic studies.

Nanomedicine is understood to have a very high potential of growth and commercialisation in this diagnostics sector as quicker market launch is possible since a regulatory framework for medical devices is not as stringent as it is for drug launch. The other reason for growth is due to a huge potential in the miniaturised device market which also allows higher volume manufacturing which will drive the production costs down.

2. Drug delivery
The pharmaceutical sector is looking for huge radical innovations in light of challenges from the generic companies and competition from biopharmaceuticals. The sector is highly regulated and needs extensive clinical trials, thus making the product launch pipeline long and at the same time reducing the chances of product success. All these make it a high-risk, high-impact sector. The rise of a new small molecule approach as well as a rise in medium molecule drugs has increased a demand in these sectors for novel drug delivery method with very specific carrier properties. Nanobiosciences and nanomedicine are uniquely placed to address drug delivery issues in the pharmaceutical market along with improving and expanding the markets in biologicals.

Here, the nanomedicine product line includes various drug delivery carrier methods and transporter molecules, therapeutic nanoparticles and nanomaterials, targeted therapy by local drug release, activatable therapeutic or theranostic nanoparticles, magnetic particle imaging and contrast agents for imaging, luminescence-based optical contrast agents for imaging, hyperthermia applications and methods to quickly commercialise stem cell technology by using targeted drugs for initiating cell differentiation4.

3. Regenerative medicine
The field of regenerative medicine involves addressing repair, regeneration and/or replacement of damaged organs or tissue via combinatory techniques and is considered to have potentially disruptive impacts on the healthcare system with higher costs.

Academia and industry are lagging in terms of finding products that can be commercialised. Nanobiosciences offers novel smart materials designs where polymers can be made to mimic biomechanical properties of native tissue and also developing Multifunctional Extracellular Matrix Analogues (EMA) and also activating the EMAs with synthetic pro-morphogens that can readily increase the bioavailability and selectivity4. These developments can enable high throughput screening techniques. These will also enable the development of nanogradient generators for controlled drug delivery. Nanobiosciences can also bring about improvements in the field of cell therapy; a concept of using cells as ‘living drugs’. On this front nanobiosciences can potentially offer at least two product lines: delivery carrier for cells and engineering ‘patient’ specific cells.

The future of personalised medicine is here
Personalised medicine is a practice of healthcare customisation, tailored around the needs of the individual patients. A working model for such a practice should be characterised (Figure 1) by:

1. Prediction: Identifying at-risk patients at the earliest time possible.
2. Diagnosis: Earlier diagnosis which is accurate and sensitive.
3. Treatment: Targeted ‘personalised’ treatment.
4. Monitor: Tracking efficacy of the treatment.

Nanobiosciences has the potential to improve personalised medicine as it can realise the goals set for early prediction and diagnosis, followed by ‘personalised’ tailored treatment and subsequent monitoring of the patient for treatment efficacy. Nanobioscience holds the key to commercialise and streamline this process by rolling out products that can improve the methodology at every stage.

1. Prediction: Advances in nanobiosciences in development of Next Generation Sequencing (NGS) along with Genome-Wide Association Studies (GWAS) in facilitating low-cost complete genome analysis will open the gates for superior and accurate prediction and identification of atrisk patients. Most of the NGS methods rely on nanotechnology-based methods. These involve template immobilisation strategies and modified nucleotide methods along with targeted capture schemes. These techniques are nascent and at various stages of development. The market here has yet to evolve. Each of the methods has its own pros and cons.

The other important prediction service is for cancer management. Apart from genetic methods, other methodologies such as cancer metastasis modelling could be used not only for understanding cancer metastasis but also for predicting the fate of the tumours (prediction and diagnosis) and it can also double up as a cancer drug-testing platform as well as a cost-effective platform for monitoring the treatment efficacy (monitoring). These cancer metastasis modelling platforms (Figures 2 and 3) are basically silicon-based substrates with nanoscale-size features fabricated on them. Cancer cells, depending on their metastatic stage, respond to these nanoscale fabricated features in unique ways thus allowing for the characterisation of movement of cancer cells, characterising external structure morphology dependence for such movements and other studies.

2. Diagnosis: Nanobiosciences enables miniaturisation of devices which can increase the production volume and also reduce production costs, shifting the supply curve in the right direction. Carbon Nanotube Field Effect Transistors (CNTFET), Silicon Nanowire Field Effect Transistors (SiNWFET), Micro Electrode Arrays (MEAs) along with DNA-Field Effect Transistors make good candidates for biosensors, for diagnostics purposes. These along with conventional MOS-FET technologies of the electronics industry can bring sweeping changes in the biomedical instrumentation sector. Microelectromechanical Systems (MEMS) and microfluidic systems will also lead to radical innovations that will usher in changes in the bioinstrumentation market dynamics. These changes can help realise point of care diagnosis.

3 Treatment: Nanomedicine holds the potential to introduce products which can improve the drug specificity, drug delivery efficiency and can also be patient-specific in its approach due to the advancements in the field of regenerative medicine by nanotechnology. Cell therapy, biomarkers, synthetic pro-morphogen-activated extra-cellular matrix analogues (EMA) can bring in patient-specific customisation to personalised medicine4.

4. Monitoring: Advancement in the field effect transistor development, improvement in the microelectrode fabrication, optimisation and production of many novel biocompatible nanomaterials with unique properties, along with the development in the electronic packaging systems, allows for production of wearable, tetherless health monitoring systems/devices to become possible.

Current trends and challenges in nanobiosciences
At this point it is absolutely necessary to study and monitor the growth of nanobiosciences as a technology. Studying the patent and publication patterns, along with investment patterns gives us clues on how the nanobiosciences market is shaping up. 76.3% of the global nanomedicine publications from 1980-2004 were towards drug delivery. Nanomedicine-based drug delivery also leads the worldwide patent applications from 1993 to 2003 at 58.8%6,7. In vitro diagnostics was the next biggest sector with 11% and 14% for publications and patents respectively for the same period6,7. In vivo imaging was 4.2% and 12.7% and biomaterials sector was 5.9% and 8% for publications and patents7.

According to a report published in 20087, which looked into the company profiles involved in the nanomedicine activity, 44% of the total businesses were start-ups and 32% were SMEs. Only 21% was contributed by the large pharmaceutical or medical device companies. This pattern of relative proportions of start-ups, SMEs and major corporates holds true for both European and US markets. As of 2008, 56% of these companies were involved in drug delivery development (matches the trends observed in publications and patents). Similarly, 16% of the companies were involved in in vitro diagnostics, which also approximately corresponds to the patent trends. 15% of the companies were into implants development. In vivo imaging and active implants made up 6% and 3% of the companies respectively, with drug development making up remaining 4%.

Despite the global recession in 2008-09, the global nanomedicine sector was worth $53 billion in 2009, with a growth rate of 13.5% and it is predicted to surpass the $100 billion mark in 20148. It is a paradox that though industry recognises the immense potential of nanobiosciences, only a fraction of total investments and developments of nanobiosciences come from big corporate businesses such as big pharmaceutical and medical device manufacturing companies (only 21% of the total market share is of the bigger businesses). The innovation and market is mostly driven by startups and SMEs. This is one of the biggest challenges for a nanobiosciences innovator; to attract more investments from bigger players. Markets attracting big businesses is a sign of a healthy and developing market with huge potential. This issue can be addressed by having a holistic approach in designing the roadmap. The current roadmaps only recognise various sectors where nanobiosciences have potential to bring about a drastic change. These sectors are mainly diagnostics, drug delivery and therapeutics. The roadmaps for each of these sectors are independent of each other, the investments are skewed (56% of the market is into drug delivery), therefore resulting innovation and market translations is not up to the mark to attract big businesses.

If we analyse the patents and publications trend data and nanomedicine market sector data in the light of parallel development of semi-conductor industry, we may be able to understand the skewed growth pattern of the nanobiosciences market. In the process of chasing Moore’s law, Intel and IBM aggressively reduced the transistor size (chip size) to smaller scales. Along with it they also improved upon various nanofabrication methods and testing different nanomaterials. Though this was spread over many decades, its effects were spilling over into other sectors mostly during the 1990s. At that point, nanodiagnostics, nanosensors for healthcare were nascent technologies. But pharmaceutical industry was well established since long before that period and drug delivery was an issue which pharmaceutical companies were long trying to optimise. Nanotechnology had a lot to offer to address the drug delivery issues. Therefore the drug delivery sector within the nanomedicine market got a head start. Because these are related to the pharmaceuticals, they have a longer production pipeline, regulatory issues, possible toxic effects, all resulting in a low success rate. This spilled over to other sectors and is discouraging big companies from entering nanomedicine market in a big way. But as the nanotechnology potential is undeniable, most of the market was taken up by start-up and SMEs.

This holistic approach involves identifying one common goal for all the three major sectors within the nanomedicine market. Personalised medicine can be that one common goal that binds all the three. This holistic approach will help in creating an ‘ecosystem’ of related cross-sector techniques under one umbrella system where a patient can get complete start to end personalised solutions from prediction, to better diagnosis and treatment followed by monitoring recovery. As part of this approach, companies, in a bid to consolidate markets, must invest wisely across the sectors. For example, diagnostics have lesser regulatory hassle and shorter product development pipeline and therefore are excellent candidates for near future investments. In the same way, investing wisely in one of the nanotechnology-inspired next generation sequencing will help in consolidating the cheaper genome sequencing market. Most in the drug delivery sector must be treated like any other pharmaceutical product and must follow similar investment patterns as that of a drug development. As far as therapeutics is concerned, it will take longer for these to be big in the market. These can be considered for long term investments. If companies wisely invest across these sectors, then they can get a chance to consolidate the personalised medicine market and get a head start in developing an ‘ecosystem’ of solutions for prediction, early diagnosis, treatments and monitoring recovery.

Identifying market needs: an example
The lifescience instrumentation market is huge with $10,150 million worth of market size in 2010 and is projected to increase to $11,379 million by 20129. It is one of the industry classifications that can be greatly improved by nanotechnology. Currently, the biggest sector within lifescience instrumentation market is PCR, with 23% market share, while electrophysiology/patch clamps is the smallest sector at 0.7%. These markets, depending on the product type, are largely driven by three factors: initial systems, services and aftermarket sale. The market share based on product type is heavy on aftermarket products at 61%, which are basically kits and reagents. Initial systems has a market share of 31% and involves buying the tool/device and its set up. The remaining 8% is the market share of services. PCRs have the highest market share because they are not initial systems intensive; they are heavy on aftermarket sales of reagents and kits. On the other hand, patch clamps have a low market share as they are more initial systems intensive. As these patch clamps are relatively more expensively, the market penetration potential is reduced. How can one improve the market share of patch clamps by redesigning the device?

The best method to increase the market share is to first reduce the expense in such a way that it increases the market penetration. This can be done by making it more ‘aftermarket sales’ intensive. This will not only drive the sales up but also greatly improves market penetration. The product can be made ‘aftermarket’ intensive by packaging the complete device as a very inexpensive, accurate, one-time use, disposable platform. Packaging it in such a way will allow one to use these devices as a diagnostics tool, which is much more useful than in its current form.

Nanotechnology’s advent helps in realising such goals and market needs by driving the prices down by changing the strategy of packaging the device as a one-time use and throw device. Patch clamps are very elaborate and sophisticated so cannot be made into a one-time use and throw device. But with nanotechnology we can make devices better than patch clamps with superior performance10 by using Silicon Nanowire Field Effect Transistors, or carbon nanotube field effect transistors and other nanoscale structure based field effect transistor. These kinds of superior miniaturisation of medical devices are one of the hot beds for innovations and investments.

Conclusion
Nanotechnology is the future of personalised medicine, where it becomes a ubiquitous technology and results in providing inexpensive, customised wholesome healthcare.

 


Abhishek Gottipati holds a master’s degree in Biotechnology from Jawaharlal Nehru Technological University, Hyderabad, India and is currently enrolled into the PhD programme at the College of Nanoscale Science and Engineering, University at Albany, Albany, NY. His area of interest is nanobiosciences with specific focus on studying carbon nanotube-cell interactions.

Joseph M. Sanders is an undergraduate studying Nanoscience at the College of Nanoscale Science and Engineering, University at Albany, Albany, NY. His areas of interest are nanobiosciences and nanoengineering.

Dr Scott Tenenbaum is an expert in the field of RNA technologies and is a trained microbiologist. He graduated with a PhD from Tulane University and worked as a post-doctoral fellow at Duke University. He is an entrepreneur, having started ‘Hocus-Locus’ based on the technologies he developed. He has an innate understanding of bringing technologies developed in laboratories into the market.

References
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2 What It Is and How It Works. The National Nanotechnology Initiative. www.nano.gov/ nanotech-101/what.

3 Bawa, R et al. Protecting New Ideas and Inventions in Nanomedicine with Patents. Nanomedicine: Nanotechnology, Biology and Medicine 1(2), 150-158(2005).

4 Roadmaps to Nanomedicine towards 2020. Joint European Commission/ ETP Nanomedicine Expert Report, (2009).

5 Vision Paper and Basis for a Strategic Research Agenda for Nanomedicine. European Technology Platform on Nanomedicine (ETP Nanomedicine), Nanotechnology for Health (2005).

6 Valentina Morigi et al. Nanotechnology in Medicine: From Inception to Market Domination. Journal of Drug Delivery (2012).

7 JRC European Commission, Joint Research Centre. Nanomedicine: Drivers for Development and Possible Impacts (2008).

8 BCC Research. Nanotechnology in Medical Applications: The Global Market (2010).

9 The IBO Industry Forecast for 2011. Instrument Business Outlook, Strategic Information for the Analytical and Life Science Instruments Industry (2011).

10 Bozhi, Tian et al. Three- Dimensional, Flexible Nanoscale Field-Effect Transistors as Localized Bioprobes. Science Vol: 329 (830-834)(2010).