Nanotechnology & Nanomedicine – a detailed overview
Nanotechnology, defined as the multidisciplinary field that aims to control matter at the atomic and molecular levels. This word was used for the first time by Professor Norio Taniguchi in 1974, even though ideas and concepts behind nanoscience had already been theorised in the famous lecture given by the Nobel prize physicist Richard Feynman during the American Physical Society meeting at the California Institute of Technology (CalTech) on December 29th, 1959. [1, 2]
In his speech, entitled “There’s Plenty of Room at the Bottom,” Feynman already supported the idea that “When we get to the very, very small world…we have a lot of new things that would happen that represent completely new opportunities for design.” [3] Nonetheless, the first applications of modern nanotechnology were accomplished only in the ’80s of the last century with the invention of two instruments, Scanning Tunneling Microscope (STM) and Atomic Force Microscope (AFM). These were essential tools that paved the way for imaging at the atomic level and manipulation of individual atoms. [1]
The main advantages of nanostructures are their small size and the high surface to volume ratio, which implies high packing density and strong lateral interactions. The fundamental difference with microstructures relies on the physical behaviour of nanostructures, whose magnetic and electric properties are determined by quantum mechanics. [4] The mentioned features make nanotechnology suitable for applications in any field, ranging from the energy sector to the environmental one, passing through electronics and food production and ending with cosmetics.
Among the areas of interest, a fundamental role of nanotechnology lies in medicine, which could be easily expected since the main components of the living cells are at the nanoscale level. [1] Nanomedicine, defined as “the science and technology of diagnosing, treating, and preventing disease and traumatic injury, of relieving pain, and of preserving and improving human health, using molecular tools and molecular knowledge of the human body” by the Medical Standing Committee of the European Science Foundation (ESF) in 2004. The five main sub-areas of nanomedicine: analytical tools, nanoimaging, nanomaterials and nanodevices, novel therapeutics and drug delivery systems, and clinical, regulatory, and toxicological issues. [5]
Among the mentioned applications, a key role is played by the formulation of drugs at the nanoscale. This kind of delivery ensures higher drug stability, decreased clearance rates, and longer circulation time, improved solubility, and the possibility of higher selectivity, thanks to active targeting through functionalization of the carriers. [6, 7] However, large companies are sometimes unwilling to invest in the research and development of nanomedicines because of concerns on their safety and uncertainties about the regulation to be applied to this kind of technique. [8, 9] Nonetheless, since the first nanotherapeutic gained clinical approval in 1995, 50 other nanoparticle-based drugs have entered clinical practice in the following two decades. [7]
Steps that a drug must undergo before entering the market: from the discovery to the registration approval passing through formulation optimisation and several clinical trials. On average, for ~10´000 compounds evaluated in preclinical studies, about five compounds enter clinical trials and only one compound finally receives regulatory approval by the US Food and Drug Administration (FDA). In the U.S. the meantime from the synthesis of a new compound to marketing approval is 14.2 years. (Thanks to Schio et al., 2017)
While a significant part of approved nanomedicines is nanoformulations of already existing drugs, increasing interest is also located in nanoformulations of cancer chemotherapies, which are delivered in highly toxic solvents in classical medicine, as well as in antimicrobial therapy. Nevertheless, one of the most exciting aspects is the possibility to translate novel therapies like nucleic acids (including siRNA, antisense RNA, shRNA, miRNA, gene delivery) into clinical applications. [7] In particular, the possibility of altering gene expression in vivo by miRNA selective delivery for therapeutic purposes is a challenging task; the development of suitable nanocarriers for miRNA delivery is, in fact, a hot topic, which has raised increasing attention in the last two decades.
Another of the fields, as mentioned above of nanomedicine that is currently under development is the use of nanotechnologies in diagnostics and imaging. Molecular imaging allows the measurement of biological processes at the cellular or molecular level. It includes several techniques, like optical bioluminescence, optical fluorescence, targeted ultrasound, molecular magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), single-photon-emission computed tomography (SPECT), and positron emission tomography (PET). The advantages in using nanoparticles (NPs) instead of single molecule-based contrast agents rely on an improvement of the image contrast, longer circulation time and the possibility of carrying higher payloads. [1, 12]
A great novelty brought by nanotechnology in health is a combination of the two applications just described. NP-based imaging and therapy have been separately investigated as just explained, but the use of multifunctional nanoplatforms allowed the simultaneous delivery of therapeutic, targeting and imaging agents. This new discipline is called theranostics, which is indeed a new term coined for NPs used for simultaneous diagnosis and treatment, and it can be attributed initially to Funkhouser approximately ten years ago. [13-16]
Theranostics significantly contributed to the growing field of personalised medicine. These dual-purpose nanomaterials used for contemporaneous diagnosis and therapy can provide hints on the site of accumulation of the therapeutic agent, either controlling its ability to reach the given target or the ability to avoid accumulation in potentially healthy tissues. This possibility of drug monitoring allows the establishment of the right doses, recognition of negative side effects at the early stages of therapy and real-time monitoring of the therapeutic response of the patient. [14, 16- 18]
References:
[1] S. Kargozar and M. Mozafari, “Nanotechnology and Nanomedicine: Start small, think big,” Materials Today: Proceedings, no. 5, p. 15492–15500, 2018.[2] U. S. N. N. Initiative, “National Nanotechnology Initiative,” [Online]. Available: https://www.nano.gov. [Accessed October 2018].[3] R. P. Feynman, “Plenty of Room at the Bottom,” in American Physical Society meeting, Pasadena, 1959.[4] G. Whitesides and P. Alivisatos, “Fundamental Scientific Issues for Nanotechnology.,” in Nanotechnology Research Directions: IWGN Workshop Report. Dordrecht, Springer, 2000, pp. 1-24.[5] T. J. Webster, “Nanomedicine: what’s in a definition?” International Journal of Nanomedicine, vol. I, no. 2, pp. 115-116, 2006.[6] I. Fernandez-Piñeiro, I. Badiola and A. Sanchez, “Nanocarriers for microRNA delivery in cancer medicine,” Biotechnology Advances, no. 35, pp. 350-360, 2017.[7] J. M. Caster, A. N. Patel, T. Zhang and A. Wang, “Investigational nanomedicines in2016: a review of nanotherapeutics currently undergoing clinical trials,” WIREs Nanomed Nanobiotechnol, vol. 9, 2017.[8] L. Jin, X. Zeng, M. Liu, Y. Deng and N. He, “Current Progress in Gene Delivery Technology based on Chemical methods,” Theranostics, vol. 4, no. 3, pp. 240-255, 2014.[9] Boisseau and B. Loubaton, “Nanomedicine, nanotechnology in medicine,” C. R. Physique, vol. 12, p. 620–636, 2011.[10] L. Schio, Strategies for Drug Discovery: New paradigms in Oncology & eADMET properties optimization Perspectives, ENSCP Paris, 2017.[11] J. K. Willmann, N. van Bruggen, L. M. Dinkelborg and S. S. Gambhir, “Molecular imaging in drug development,” Nature Reviews Drug Discovery, vol. 7, July 2008.[12] W. Cai and X. Chen, “Nanoplatforms for Targeted Molecular Imaging in Living Subjects,” Small, vol. 3, no. 11, pp. 1840-1854, 2007.[13] S. M. Janib, A. S. Moses and J. A. MacKay, “Imaging and drug delivery using theranostic nanoparticles,” Advanced Drug Delivery Reviews, vol. 62, pp. 1052- 1063, 2010.[14] J. Xie, S. Lee and X. Chen, “Nanoparticle-based theranostic agents,” Advanced Drug Delivery Reviews, vol. 62, pp. 1064-1079, 2010.[15] T. L. Doane and C. Burda, “The unique role of nanoparticles in nanomedicine: imaging, drug delivery and therapyw,” Chem. Soc. Rev., vol. 41, p. 2885–2911, 2012.[16] N. Ahmed, H. Fessi and A. Elaissari, “Theranostic applications of nanoparticles in cancer,” Drug Discovery Today, vol. 17, no. 17/18, 2012.[17] J. H. Ryu, S. Lee, S. Son, S. H. Kim, J. F. Leary, K. Choi and I. C. Kwon, “Theranostic nanoparticles for future personalized medicine,” Journal of Controlled Release, vol. 190, pp. 477-484, 2014.[18] L. Y. Rizzo, B. Theek, G. Storm, F. Kiessling and T. Lammers, “Recent progress in nanomedicine: therapeutic, diagnostic and theranostic applications,” Current Opinion in Biotechnology, vol. 24, pp. 1159-1166, 2013.Now that you have read about Nanotechnology & Nanomedicine. Check out our course on Ampersand Academy Read this interesting article about Thermogravimetric Analysis.