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Nanotechnology in cancer care - what's on the horizon?

Clare Sansom reports from Nano World Cancer Day: London 2017

Nanotechnology can be defined simply as science, technology and engineering conducted at the nanoscale: that is the scale of the exceptionally small. It is generally assumed to cover objects from approximately one to 100 nanometres (10-9 to 10-7m) in length. This increasingly important branch of technology is now being applied to many therapeutic areas, with oncology perhaps the most advanced. Nano World Cancer Day, held on 2 February at the University of Liverpool’s headquarters in central London, showcased recent developments in nanotechnology that should soon begin to benefit cancer patients.

This London meeting was one of 15 held simultaneously across Europe, including several countries outside the EU. The whole event was organised jointly by the European Technology Platform for Nanomedicine (ETPN) and a Horizon 2020 project, ENATRANS (Enabling NAnomedicine TRANSlation).  Each meeting was introduced with the same welcome video from the chair of ETPN, Patrick Boisseau, who briefly explained how nanotechnology is benefiting cancer patients; this is, however, still an area of significant unmet medical need.

The welcome video was incorporated into a short presentation that outlined the scale and nature of the industry in Europe and neighbouring countries. Over 2000 companies and organisations in the region are involved in nanomedicine, and about 120 of these are full members of the ETPN. It recently published a detailed strategy for incorporating nanotechnology into healthcare that covers the period 2016-2030 and includes oncology among its highlighted disciplines.

Four main speakers from academia and industry gave research presentations outlining applications of nanotechnology with direct, if not immediate, relevance to oncologists and their patients. The first of these was Prof. Khuloud Al-Jamal from the Institute of Pharmaceutical Science at King’s College London, who presented novel applications of magnetically targeted nanoparticles for diagnostics and therapy. Conventional small-molecule drugs are generally difficult to direct to the site of a tumour and so must be given in higher than optimum concentrations, potentially leading to systemic side-effects. Stable, non-toxic superparamagnetic iron oxide nanoparticles (SPIONs) are strongly attracted to magnetic fields but have no residual magnetism and can be directed to tumour sites to deliver drugs or imaging contrast agents. Particles of this size tend to accumulate in the tumour rather than the surrounding tissue; this effect, known as enhanced permeability and retention (EPR), follows naturally from the ‘leaky’ nature of the fast-growing tumour vasculature.

Prof. Al-Jamal and her team have now developed a novel type of nanoparticle, the polymeric magnetic nanocapsule (m-NC), that has an oil core, a polymeric shell and a hydrophilic coating and that circulates in the bloodstream for longer than conventional SPIONs. These can carry a variable and finely tuneable payload of SPIONs and therapeutic or contrast agents to a tumour site. The group found that these particles could deliver docetaxel effectively to a CT26 colon carcinoma embedded in a mouse flank, and that delivery was greatly enhanced if an external source of magnetic field had been applied to the tumour. The drug doses that were injected were so high that they would have been fatal if given in a free drug form. Mathematical models have shown that this magnetic targeting concept could be extrapolated to treat human patients.

Professor Andrew Miller, a visiting professor at King’s College London at the Institute of Pharmaceutical Science and founding director of KP Therapeutics was the next to speak. His company has a lipid-based nanoparticle platform technology that carries a payload of drug and/or imaging agent(s), assembles spontaneously in aqueous solution and will accumulate in tumour tissue through the EPR effect. These nanoparticles have a typical ‘ABCD’ design, where the innermost layer, A, is the active pharmaceutical ingredient; B, a protective compaction/association layer (lipid in this case); C, a polymer layer designed to increase biocompatibility; and D, a biological targeting layer that recognises and binds to the desired target.

Professor Miller and his colleagues are currently developing a ‘precision therapeutics approach’ for cancer treatment that uses their nanoparticles in combination with focused ultrasound, which raises the local temperature of irradiated cancer tissue to 41-42oC.  This local hyperthermia effect results in a substantial increase in the permeability in tumour blood vessels and thus enables their nanoparticles to concentrate almost entirely in the tumour, giving much more tightly focused drug delivery. The combination of these nanoparticles and focused ultrasound could be very useful to target anticancer drugs to tumours and the company is now preparing for clinical development. Professor Miller concluded his talk by introducing a novel needle-free method of sublingual nanoparticle delivery by nanofibrous mucoadhesive patch technology that is being developed in collaboration with teams in the Czech Republic. This method is being applied to vaccination nanoparticles and could also be used to deliver ‘anti-cancer vaccines’.

Dr Dan Gooding of Nuformix, a ‘micro-SME’ based in Cambridge, UK, described a novel method of re-purposing known small-molecule drugs including oncology drugs by re-engineering their crystalline forms. Crystallising a pharmaceutically active compound with a second, inert and non-toxic one will produce a substance with identical pharmacology but very different physical properties. These new physical properties can uniquely enable the creation of new drug products, for example in new delivery formats, in new indications or for new geographic markets. Regulatory agencies can rely on existing safety data to support future product approvals unlike in the case of novel chemical entities, enabling products containing cocrystal forms of known drugs to move more rapidly towards patients and the market. Crucially, the alterations to the drug substance are significant enough to be protected with new ‘substance of matter’ patents. Two of Nuformix’ first three re-formulated products to enter clinical development are in oncology.

The final research presentation was given by Dr Gareth Wakefield of Xerion Healthcare, a newly-formed company based near Oxford. He described a novel nanoparticle-based method for making radiotherapy, which is currently used to treat about 40% of cancer patients in the UK, more effective. The high-energy X-rays used in radiotherapy machines generate free radicals in the irradiated site and these destroy the surrounding cells. Unfortunately, however, most tumours contain regions that are low in oxygen and generate few free radicals. This dormant, hypoxic tissue responds poorly to radiotherapy and can seed tumour re-growth after treatment ends. Xerion’s solution to this problem uses titanium dioxide nanoparticles, which will interact with X-rays to form free radicals in the absence of oxygen and thus allow the radiation to kill hypoxic tumour tissue. This treatment has been shown to be effective in a mouse model of head and neck cancer and the first clinical trials are being planned. The protocol will involve injecting the nanoparticles directly into the tumour before a standard radiotherapy regimen.

The meeting also included short presentations from Dr Euvian Tan of the Nanomedicine Translation Advisory Board (NanomedTAB) and from Dr Jess Sutcliffe of Cancer Research UK. Dr Tan described the role of the NanomedTAB, which offers free mentorship to any European researcher in nanomedicine who is seeking to advance a product or research idea into commercial development. There is a rolling online application process to access this service: the next deadline is 28th February 2017, with the next “TAB-In” session being held in London on 4th April 2017 to coincide with the forthcoming European Nanomedicine Meeting.  Dr Sutcliffe spoke about Cancer Research UK’s Pioneer Award.  This offers funding for early stage ideas to any researcher or consortium with a novel research idea of relevance to an ‘intractable problem’ in cancer. There are three closing dates each year, the next being 24th April 2017.  Applications are welcome from all disciplines and from scientists at any stage of their career, and international collaborators can also be included. Sutcliffe ended by highlighting two nanomedicine products in development: one for early cancer detection – Owlstone Medical’s Breathalyzer -  and another for using so-called ‘nano-bubbles’ to re-oxygenate intractable pancreatic tumours.

The meeting was sponsored by Precision Nanosystems, a Canadian company that has developed a novel microfluidic technique for the manufacture of finely tuned, lipid-based nanoparticles for medical applications. Its versatile products are available at both lab bench and industrial scales.

Nano World Cancer Day is now a yearly fixture in the calendar, linked to and coinciding with World Cancer Day on 4th February. This is a fast-moving research area and we can expect that significant progress will be reported at the equivalent meeting in 2018.



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