N ANOPARTICLES IN BIOLOGY AND MEDICINE Antti Rautiainen KE Nanopartikkelit

I NTRODUCTION Nanoparticles have unique size-dependant physical properties (arising from surface-to-volume ratio) which can be very useful in biology and medicine Biology: analyzing methods, diagnostics Medicine: dianostics and care/therapy, ”Nanomedicine” Understanding of biological processes on the nanoscale level is a strong driving force behind development of nanotechnology 24 nanotechnology based therapeutic products have been approved for clinical use, with total sales exceeding 5,4 billion $ (80 % from nanoparticle based drug delivery systems) (2008)

A PPLICATIONS Fluorescent biological labels Drug and gene delivery Bio detection of pathogens Probing of DNA structure Tissue engineering Tumour destruction via heating Separation and purification of biological molecules and cells MRI contrast enhancement Phagokinetic studies

N ANOPARTICLES IN MEDICINE / BIOLOGY Two examples Nanovesicles: drug delivery, membrane filled with drug, membrane from polymeric material Quantum dots: imaging, metal nanoparticles (e.g. iron oxide), precise control of the average particle size and a narrow distribution of sizes allow creating very efficient fluorescent probes that emtit narrow light in a very wide range of wavelengths  for example very precise protein identification Hundreds of applications proposed/introduced

W HY USE NANOPARTICLES IN MEDICINE ( A LITTLE BIT OF DEEPER POINT OF VIEW )? Nanoparticles allow to modify fundamentals properties in biological environmet Solubility Diffusivity Blood circulation half-life Drug release characteristics Immunogenenicity More effective, more convenient routes of administration, lower therapeutic toxicity, extend the product life cycle, reduce healthcare costs Typical configurations utilised in nano-bio materials applied to medical or biological problems.

D IAGNOSTICS Nanoparticles allow detection on the molecular scale Identification of abnormalities such as fragments of viruses, precancerous cells and disease markers that cannot be detected with tradional diagnostics Nanoparticles enhance imaging contrast of tradional medical imaging (specially MRI) Use of superparamagnetic nanoparticles Enhanced sensitivity and specifity

D RUG DELIVERY Nanoparticles can be used to Enhance solubility of poorly water-soluble drugs Prolong the half-life of drug systemic circulation by reducing immunogenecity Release of drugs at a sustained rate or in an environmentally responsive manner  lower frequency of administration Delivery of drugs in a target manner to minimize systemic side side effects Delivery of two or more drugs simultaneously for combination therapy to generate a synergistic effect and suppress drug resistance Schematic illustration of therapeutic nanoparticle platforms in preclinical development: (a) liposome, (b) polymer–drug conjugate, (c) polymeric nanoparticle, (d) dendrimer, and (e) iron oxide nanoparticle. The red dots represent hydrophilic drugs and the blue dots represent hydrophobic drugs.

S OMETHING GOOD, SOMETHING BAD Nanotoxicology A little of information available on effects of nanoparticles on environment, health and safety Mostly on carbon nanotubes Nanotoxicology relies on many analytical methods for characterization of nanomaterials as well as their impacts on in vitro and in vivo function TEM, elemental analysis, fluorescence spectroscopy, proliferation assays, necrosis/apoptosis assays, DNA damage assays,oxidative stress, etc. During in vivo biodistribution studies, organ morphology is often examined. In this example, excised kidneys from mice after copper exposure with (a) 17 mm diameter particles, (b) 23.5 nm diameter particles, and (c) control conditions are shown. (Reprinted with permission from ref Copyright 2006, Elsevier.)

C ONCLUSION Nanoparticles may (and will) increase knowledge of biological systems and diseases, improve medical diagnostic and enable to cure some diseases that can’t be cured with tradional methods (AIDS, cancer etc.) Understanding of biological systems combined with knowledge of physics/chemistry/engineering will give new points of view to tradional medicine When? 10 years, 20 years? Today

R EFERENCES OV Salata. ” Applications of nanoparticles in biology and medicine”. Journal of nanobiotechnology. Vol. 2: L Zhang et. al. ” Nanoparticles in medicine: Therapeutic applications and developments ”. Clinical pharmacology&Therapeutics. Vol. 83: K Dreher. ” Health and environmental impact of nanotechnology: Toxicological Assessment of manufactured nanoparticles ”. Toxicological sciences. Vol B Marquis et. al. ” Analytical methods to assess nanoparticle toxicity ”. Advance Article on the web