Written by Jonathan Dalla-Riva
Jonathan Dalla-Riva is a Medical Writer at Alpharmaxim Healthcare Communications
It was the irrepressible mind of Nobel prize-winning physicist Richard Feynman that, way back in the late 1950s, dreamt up the notion of molecular machines that could be used to manipulate matter at the atomic level. Feynman’s idea that a patient might one day be able to “swallow the surgeon” represents the first ambitious vision of nanomedicine.1 Over 30 years later, Doxil®, a chemotherapeutic agent used for the treatment of several different cancers, became the first nanomedicine to be approved by the FDA for clinical use. By 2017 there were 50 FDA-approved nanodrugs on the market.2
Specifically, nanotechnology deals with materials at a scale of 1 to 100 nm; that is, in the range of a billionth of a metre. But why is smaller better when it comes to medical treatments? Fundamentally, many of the limitations and drawbacks of standard therapeutics can be overcome by the unique physiochemical properties that emerge at the nanoscale. Easier tissue accessibility, greater tissue selectivity and facilitation of sustained drug release are features of nanomaterials that confer enhanced efficacy and reduced toxicity.2 In the case of currently available nanodrugs, this has involved the coupling of already-approved drugs to programmable nanoparticles, such as liposomes, polymers or metal oxides.3 The clearest example of these benefits can be found in the treatment of cancer, where nanoparticles allow increased delivery of chemotherapeutic agents directly to the tumour, thereby reducing drug toxicity.2
…many of the limitations and drawbacks of standard therapeutics can be overcome by the unique physiochemical properties that emerge at the nanoscale.
Here at Alpharmaxim, our recent work with ONPATTRO®, the first RNAi therapeutic to be approved in the US and Europe, has given us first-hand experience of how nanomedicine is revolutionising healthcare. Formulated as lipid nanoparticles for delivery directly to hepatocytes, ONPATTRO® is specifically targeted to the liver, where it leads to a reduction in the disease-causing mutant transthyretin protein. Through this mode of action, progression of the debilitating symptoms associated with hereditary transthyretin amyloidosis can be halted.4
While currently available nanomedicines are largely limited to drug-carrying nanoparticles, research and development in the field of nanomedicine is continuing to advance at a rapid pace. Potential applications include novel antimicrobials, implantable biosensors, biocompatible tissue implants and the possibility to perform exquisitely detailed diagnostic imaging. In fact, nanomedicine lies at the heart of the new field of theranostics, which is concerned with producing diagnostic and therapeutic agents that are combined into a single entity to allow for a more individualised disease treatment.3
Despite the exciting potential and ongoing investment in nanomedicine, unpredictable safety issues with these unprecedented technologies present a major regulatory challenge. To clear the path to clinical approval, the timely development of well-defined national and international guidelines for the development and characterisation of nanodrugs is needed.3 Nevertheless, research in nanomedicine continues apace, and it even looks like medical nanorobots are on the horizon. A recently published study in Nature Biotechnology used DNA origami to construct an autonomous DNA robot. Upon recognising tumour-associated cells, this nanorobot released its therapeutic cargo specifically at the tumour site, leading to cancer cell death and inhibition of tumour growth in the mouse model.5 We may have to wait a little longer before such treatments are available in the clinic, but the realisation of Feynman’s dream of nanosurgery is beginning to look ever more likely.
1. Freitas RA, Jr. What is nanomedicine? Nanomedicine 2005;1(1):2–9
2. Ventola CL. Progress in nanomedicine: approved and investigational nanodrugs. Pharmacy and Therapeutics 2017;42(12):742–755
3. Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology 2018;16(1):71
4. Adams D, Gonzalez-Duarte A, O’Riordan WD, et al. Patisiran, an RNAi therapeutic, for hereditary transthyretin amyloidosis. N Engl J Med 2018;379(1):11–21
5. Li S, Jiang Q, Liu S, et al. A DNA nanorobot functions as a cancer therapeutic in response to a molecular trigger in vivo. Nat Biotechnol 2018;36(3):258–264