Author: Ruth Sang Jones Edited by: Burcu Anil Kirmizitas
The development of humankind has always been tracked by its knowledge on the manipulation of certain materials, with early humans advancing from stone to bronze and iron over the expanse of several thousand years. The onset of the digital world and its predominance in daily life has prioritised ‘the information age’ as a common descriptor of the modern era. Yet, in the background, the revolution in materials is still ongoing, with one of the primary objectives being to engineer at the nanoscale in order to exploit novel material properties of that magnitude. Nanomaterials, synthesised either by top-down or bottom-up approaches, have at least one dimension in the nanometre size, i.e. 1 billionth of a metre. The commonly defined upper size limit is ~100 nm, below which size effects bring about changes in physical and chemical properties in comparison to bulk. Experts in the field of nanoscience can agree that the onset of the nano-age is not yet upon us, but short-term and long-term advances may one day bring applied nanomaterials to the everyday human-material interchange. Even now, 1600+ consumer products have been manufacture-identified as involving nanotechnology, according to a consumer product inventory published in 2015.
One of the areas nanomaterials is expected to transform is medicine, thus creating the field of nanomedicine. The predicted potential of nanomaterials in medicine is wide-range, covering both disease diagnosis and treatment. Drug delivery is deemed as a promising domain for use of nanomaterials such as nanoparticles or even nanotubes to act as vehicles for carriage of drugs to targeted sites in the body. It is also important to note that nanomedicine does not only consider inorganic or metallic nanomaterials, but a bulk of studies focus on polymeric, liposomal or protein based nanoparticles, also classed as such because of their size. Nanoparticles also show promise as MRI contrast agents that can enhance medical imaging. Furthermore, thanks to their mechanical properties, nanomaterials are considered for growing cell and tissue scaffolds. There is also a capacity for them to be used in wear-resistant, biocompatible medical implants. Further development in nanoelectronics opens up the possibility of bio-sensors or even artificial retinas or cochleae. These applications are more complex than other already established uses, such as titanium dioxide or zinc oxide nanoparticle incorporation into sunscreens to protect skin from UV light irradiation.
The predicted benefits of nanomaterial omnipresence have attracted the attention of governments and private investors, with expenditure on R&D soaring worldwide. According to a report endorsed by the Royal Society and the Royal Society of Engineering titled ‘Nanoscience & Nanotechnologies; opportunities and uncertainties’, the UK government pledged £45 million per year for the period spanning 2003-2009, with total European funding reaching ~ 1 billion euros. However, there is an evident tendency for interested parties to exaggerate the extent of progress in the field. As an example, the US National Nanotechnology Initiative predicted that nanotechnology would be capable of detecting and eliminating early stage cancerous tumours by the year 2015, thus ending death by cancer. Such bold claims have yet to be realised, bringing into question the real up-to-date level of nanotechnology development. What is the innovative output from the R&D expenditure? Based on a report by the Knowledge Transfer Network issued in 2010, there were ~ 100 nanomaterials companies based in the UK alone in that year, with ~30 of these involved in medical device or drug delivery market applications. Yet the accessibility of their products is low, as many potential nanomedicines are still undergoing trial stages and need to be subjected to rigorous regulatory protocols, which themselves must undergo reviewing as new research surfaces. In the US, 51 nanomedicines have been approved by the FDA to date, with the nanomedicine classification applied to "therapeutic or imaging agents which comprise a nanoparticle in order to control the biodistribution, enhance the efficacy, or otherwise reduce toxicity of a drug or biologic".
Featured in this article is the nanomedicine company MagForce. It is worthy of highlighting since it is the very first in the world to receive European regulatory approval for use of nanoparticles in a commercial medical product. It has also held a place on the US FDA approval list of nanomedicines since 2010, as one of the very few metal oxide nanoparticle products on a list dominated by polymeric or liposomal particles. This statistic is very telling of the length to which nanomaterials for medical use must be assessed for toxicity and other health hazards. The product consists of iron oxide nanoparticles of average diameter 15-20 nm that are covered in a patented aminosilane coating which functions to stabilise the particles and allows their dispersal in water, forming a colloidal solution. The solution, originally developed for treatment of glioblastomas -a particularly aggressive form of brain cancer- can be directly injected into a patient’s tumour tissue. The nanoparticles can infiltrate the space around tumour cells, and are subsequently subjected to an externally applied, very rapidly alternating magnetic field. The iron oxide nanoparticles themselves have superparamagnetic properties, and thus react to the magnetic field oscillation by vibrating and releasing heat into their local environment, i.e. the tumour tissue. The result is thermal destruction of tumour cells or sensitisation for other treatments. A small volume of fluid is sufficient to deliver a high density of nanoparticles to the target site, as 1 mL contains ~17 trillions of them. The innovative intratumoral ferrofluid injection of nanoparticles is known as NanoTherm® therapy which was launched in 2011. This is coupled to the specially designed magnetic field applicator, the NanoActivator®. Generally, this overall method of treating cancer is known as magnetic hyperthermia. This technology is available at six hospitals in Germany, and has been administered to ~90 brain tumour patients and ~80 patients with other tumours. The therapy has proven successful in extending patient survival beyond what is expected, according to historical control data.
It is evident that the nanomedicine age has not fully materialised as many listed potential applications have yet to become market products. The field is still nascent but growing exponentially, with FDA registered trials of novel nanomedicines increasing threefold within the recent 3-year period. Such numbers also motivate competition within the industry. However, we must be patient whilst we wait for the real dawn of the nano-age.