The future of nano-devices in medicine Matthew Hockley, studying BSc Biomedical Science (Hons), Level 2 The University of Lincoln Introduction Nano-devices today are still thought by many as sci-fi fiction but advances over the past 20 years have started becoming non-fiction. Many advances have been made into nanomedicine for application in the medical arena in particular nanoparticle and biomarkers for drug delivery as well as self-assembling nanotechnology. A combination of both nanoparticles for drug delivery and self- assembling nanotechnology could be the building blocks for a future nano-robot device to act independently by administering xenobiotics or other treatments to target specific health problems in the human body. Nanoparticles in drug delivery are currently being developed with a promising role in medicine with improvements in localisation and specificity of drugs. Furthermore, developments into passing drugs across the blood-brain barrier are being developed. Other promising developments in nanoparticles have been designed to deliver other payloads such as light or heat which can aid in diagnosis and treatment and applications in gene delivery. Research into self-assembling nanotechnology is becoming more popular but is still very much in the developing stages. There are currently two proposed approaches to carrying out self-assembly which are the arrangements of independent atoms and molecules into a specific structure or self-assembly using biological molecules such as DNA and proteins (Muir et al., 2011). Nanoparticles in drug delivery Nanoparticles offer more advantages over common drugs by protecting premature degradation of drugs, releasing drugs to react in the localised area in the body, enhancing absorption therefore increase bioavailability and control of the pharmacokinetic profile (Peer et al., 2007). Development of nanoparticles has been designed for a variety of different medical conditions over the past few years where applications are proposed to cure HIV and many different types of cancers. A list below shows examples of different nanocarrier drugs on the market. Compound PEG-L-asparaginase Commercial Name Oncaspar Nanocarrier Polymer-protein complex Immunotoxin (fusion protein) Chemoimmunoconjugate Indications Acute Lymphoblastic leukemia Cutaneous T-cell lymphoma Acute myelogenous leukemia IL-2 fused to diphtheria toxin Anti-CD33 antibody conjugated to calicheamicin Anti-CD20 conjugated to yttrium-90 or indium-111 Ontak (Denilelukin diftitox) Mylotarg Zevalin Radioimmunoconjugate DaunoZome Abraxane Liposomes Albumin-bound paclitaxel nanopartical Relapsed or refractory, low-grade, follicular, or transformed nonHodgkin’s lymphoma Kaposi’s sarcoma Metastatic breast cancer Daunorubicin Paclitaxel Table adapted from Peer et al. (2007) Of the current 10 nanocarriers included in the global market study of nanocarriers by Cientifica (2013), 45% of nanocarriers were composed from gold nanocarriers and liposomes. As well as carrying drugs, nanoparticles can deliver other toxins which could not normally be used. An example is from a recent study which has shown a possible prevention and cure for strains CXCR4 and CCR5 tropic HIV-1 using nanoparticles loaded with melittin, bee venom (Hood et al., 2013). Furthermore, this application used for HIV-1 prevention could be applied to additional viruses such as hepatitis B and C due to action in a similar method. Nanoparticles have been designed for delivering DNA or RNA to specific tissues and cells. A study carried out in 2008 showed the capabilities of using DNA to cause suicide of epithelial ovarian cancer cells in mice (Sawicki et al., 2008). With capabilities to modify cells to proliferate or to undergo apoptosis, a nano-scaled device will need to adapt to a given medical condition such as different types of cancer by possibly undergoing self-assembly. Self-assembling nanotechnology Development of self-assembly in nanotechnology has improved over the past years with many different possibilities for applications in medicine. Self-assembly can be one of two methods which are mechanosynthesis or manipulation of existing biological components such as DNA and proteins. Mechanosynthesis is where molecular assemblers are used to construct anything from materials to biological proteins using atoms or molecules. The use of mechanosythesis is still theoretical but applications have been suggested using carbon-carbon dimer placement tool given the family name of DCB6-X (Merkle and Freitas, 2003). Compared to mechanosynthesis, self-assembly using biological components has had applications in laboratories with many different uses currently in-development. The most common type of biological components used is proteins where C-terminal and N-terminal are utilised for electrostatic self-assembly (Ji and Shen, 2005). Research has shown that using a gold nanoparticle smaller than 15nm can be used as the building block for encapsulation using self-assembling protein nanoparticles which is promising for developing biomedical devices (Yang and Burkhard, 2012). Developments combining two separate protein chains using a short synthetic peptide to form a complex have shown to have applications in the medical arena combining proteins to form an active neurotoxin drug such as botulinum (Ferrari et al., 2011; Ferrari et al., 2012). Nanoparticles have been further designed to control self-assembly of cytoskeletal structures in the body by use of magnetic nanoparticles coated with proteins which are important for control of mitosis and cell migration (Kumar, 2013). Conclusion To conclude, currently there is a lot of research that still requires development till nano-devices which can work independently in the body become common place in hospitals. With more funding being dedicated to nanotechnology, advances in nanomedicine are soon going to increase with ever growing applications and replicate the success of biotechnology. The applications of nanoparticles is growing with interest from pharmaceutical companies funding more towards developing nanoparticles for drugs which have a better bioavailability and allow more control over pharmacokinetic of a drug. The uses of nanoparticles are slow appearing to market currently due to lack of funding for clinical trials. Development into self-assembly are still in the distant future but with current developments using stapling techniques and methods for constructing structures, nano-devices that can self-assemble may appear sooner than expected. Self-assembly is only half the challenge when the self-assembly requires a certain shape or structure to cause an affect which, depending on the method used will require a lot of work and engineering. Currently, nano-devices consist of implants used for detecting cancer and sensors to diagnose a medical condition. An example of an implanted nano-device is a sensor to confirm a myocardial infarction by detecting three cardiac marker peptides which are cTnl extravasation, Myoglobin extravasation and CK-MB extravasation (Ling et al., 2011). References Cientifica Ltd. (2012) Nanotechnology for Drug Delivery: Global Market for Nanocarriers [Online] Available from: http://www.marketresearch.com/Cientifica-Ltd-v2574/Nanotechnology-DrugDelivery-Global-Nanocarriers-6856624/ [Accessed 20th March 2013] Ferrari, E., Maywood, E.S., Restani, L., Caleo, M., Pirazzini, M., Rossetto, O., Hastings, M.H., Niranjan, D., Schiavo, G., and Davletov, B. (2011) Re-assembled botulinum neurotoxin inhibits CNS functions without systemic toxicity. Toxins, 3(4), pp. 345-355. Ferrari, E., Soloviev, M., Niranjan, D., Arsenault, J., Gu, C., Vallis, Y., O'Brien, J., and Davletov, B. (2012) Assembly of protein building blocks using a short synthetic peptide. Bioconjugate Chemistry, 23(3), pp. 479-484. Hood, J.L., Jallouk, A.P., Campbell, N., Ratner, L., and Wickline, S.A. (2013) Cytolytic nanoparticles attenuate HIV-1 infectivity. Antiviral Therapy, 18(1), pp. 95-103. Ji, J. and Shen, J. (2005) Electrostatic Self-assemble and Nanomedicine. Conference Proceedings : ...Annual International Conference of the IEEE Engineering in Medicine and Biology Society.IEEE Engineering in Medicine and Biology Society.Conference, 1, pp. 720-722. Kumar, S. (2013) Microtubule assembly: Switched on with magnets. Nat Nano, 8(3), pp. 162-163. Ling, Y., Pong, T., Vassiliou, C.C., Huang, P.L., and Cima, M.J. (2011) Implantable magnetic relaxation sensors measure cumulative exposure to cardiac biomarkers. Nat Biotech, 29(3), pp. 273-277. Merkle, R.C. and Freitas, R.A.,Jr (2003) Theoretical analysis of a carbon-carbon dimer placement tool for diamond mechanosynthesis. Journal of Nanoscience and Nanotechnology, 3(4), pp. 319-324. Muir, N.C., Dudley, D., and Peterson, C. (2011) Nanotechnology For Dummies. Wiley. pp. 85-87 Peer, D., Karp, J.M., Hong, S., Farokhzad, O.C., Margalit, R., and Langer, R. (2007) Nanocarriers as an emerging platform for cancer therapy. Nature Nanotechnology, 2(12), pp. 751-760. Sawicki, J.A., Anderson, D.G., and Langer, R. (2008) Nanoparticle delivery of suicide DNA for epithelial ovarian cancer therapy. Advances in Experimental Medicine and Biology, 622, pp. 209-219. Yang, Y. and Burkhard, P. (2012) Encapsulation of gold nanoparticles into self-assembling protein nanoparticles. Journal of Nanobiotechnology, 10, pp. 42-3155-10-42.
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