NANODIAMONDS FOR BIOMEDICINE. Unique Nanodiamonds Produced by Laser from Ash & Wax

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1 NANODIAMONDS FOR BIOMEDICINE **************************************************************************************************************** Unique Nanodiamonds Produced by Laser from Ash & Wax 1

2 Ray Techniques (RT) Technologies Pioneering technology for nanodiamond synthesis Creation novel products based on nanodiamonds Our mission is to develop & provide advanced materials based on the unique nanodiamond features 2

3 Nanodiamond Structure Diamond core (sp3) with average size of ~4 nano-meters having unique diamond properties Hybrid surface structure (sp2) with unpaired electrons Active surface shell of various functional groups containing O, H and N Chemically active shells enable to attach inert tiny diamond crystals to bio-molecules and particles, to transfer them unique diamond features and to create new objects and with desired properties and functions. 3

4 Current Nanodiamond Applications FILLERS IN PAINTS, PLASTICS & RUBBERS ABRASIVES IN FINE POLISHING & LAPPING ND POWDER ADDITIVES IN COATING SOLUTIONS CVD precursor Galvanic coatings Anodizing Electroless coating Polymer films ADDITIVES IN LUBRICANTS MILITARY APPLICATIONS 4

5 Nanodiamonds Bio-Med Research: Rapidly Growing Market The first complete collection of academic papers on ND applications in biomedicine up to 2010: targeted drug and gene delivery cancer therapy bio-sensing single particle imaging in cells novel composites for implants extraction and purification of proteins According to experts in the field of ND biomedical applications, ND will be widely used in the pharmaceutical industry within 3 years. 5

6 What is Special about Nanodiamonds for Bio-Med? High chemical stability of ND nucleus and high chemical activity of its functional cover providing the outstanding ability of interaction with bio-molecules and drugs Ability to control the constancy of size and shape of agglutinates Large specific surface area and high adsorption potential Extreme mechanical hardness The highest thermal conductivity while being absolutely dielectric Possibility to be turned into a semiconductor Outstanding optical properties including photoluminescence The highest sound propagation velocity Biological compatibility and non-cytotoxicity 6

7 Next-Generation Cancer Treatment The researchers led by Dean Ho (Northwestern University in Illinois) discovered that binding drugs to ND decreased tumor resistance to drugs leading to their effective shrinkage following chemotherapy. NDs are non toxic to body tissues and are not recognized by the body s immune system as foreign. Benefits: ND can trap ~ 5 times more drugs compared to existent drug delivery Drugs can be slowly released over time (several months) ND localize drugs and minimize and mitigate side effects ND can be combined with a wide variety of drugs and RNA 7

8 Promise for Safe Gene Therapy Gene therapy promises hope for successful treatment of many diseases: severe inherited ailments - like-cystic fibrosis, hemophilia, muscular dystrophy and sickle cell anemia retinal diseases and color blindness Parkinson s disease, diabetes and cancer Major problem: efficient and safe delivery of genes to cells. Proposed solution: NANODIAMOND CARRIER Preliminary results: straight ND gene delivery into cells was found to be 70 times greater than that of a conventional standard. 8

9 Long-Lasting Implants & Prostheses Huge demand for medical implants: Cardio-defibrillators, heart valves, pacemakers, etc Orthopedic implants Intraocular lenses Cosmetic implants and many more The market for medical implant devices in the U.S. alone is estimated to be $23 billion per year and it is expected to grow by about 10 % annually for the next few years. Today the materials mostly used in medical implants are not enough biocompatible and wear resistant. THE NEW HOPE: ND coating for implants and advanced ND-polymer compositions with high biocompatibility and wear resistance. 9

10 Bio-Sensing ND has be shown to be a promising bio-sensing material: Wide working potential window due to unique diamond features Resistance to fouling Compatibility with biological fluids & non-cytotoxity Ease of surface modification Serial Gamma Scintigrams of KS Patient after Pegylated liposomes containing 111In- DTPA (remote loaded) 4 hr 24 hr 48 hr 96 hr ND is a safe alternative to toxic quantum dots! 10

11 Magnetic Resonance Imaging (MRI) MRI contrast agent to ND leads to dramatically improved signal density and vivid image contrast as per a study by Northwestern University RayND have demonstrated enhanced paramagnetism, increased amount of RPC and stronger anti-ferromagnetic exchange interaction between these RPC. RT surface modification by Fe-doping, enables producing magnetic ND. RT surface modification by heat treatment results in strong ferromagnetism of un-known nature. 11

12 Single Particle Imaging Proteins are hard to track in living bodies, but by attaching bright markers it's possible to see where they are and where they are going. Existing techniques employ fluorescent probes which can often extinguish or turn dark and may be toxic in a live body. ND can attach to proteins in the body making them easier to detect and track. ND is ideal for single particle imaging: long shelf lifetime fluorescence lasts forever no blinking behavior non-cy The market for medical implant devices in the U.S. totoxic and highly biocompatible ND can attach to proteins in the body making them easier to detect and track. (Source: Carlo Bradac, Macquarie University) 12

13 Extraction and Purification of Proteins Recombinant luciferase chromatography using ND sorbent : 1 - initial sample, 2 - freely released protein components, 3 - washing the column, the maximum fraction of the luciferase activity in the elution. The yield reached in two independent tests by one operation amounted 35 and 38% of the desired product. Bondar et al, Nanodiamonds with original properties: application in biology and medicine; 13

14 Nanodiamond (ND) Quality In biomedicine, you need ND powder of the best quality! The quality of ND is determined by: Chemical homogeneity of functional groups on the surface area Purity (metal- and graphite- free) Grain size homogeneity Absence of poly-crystals Ability to full disaggregation The quality of ND depends on the methods of ND synthesis and purification. 14

15 Where can you get high quality ND? Where does conventional ND come from? NDs used today are produced by detonation. Explosives are detonated inside metal reactors, which inevitably causes metals to penetrate the morphological structure of ND Where does RayND come from? Ray Techniques has developed a novel green laser-based technology for producing ND (RayND) We do not detonate we make our diamonds out of pure carbon soot by controlled synthesis! RayND is the most suitable ND for biomedicine! 15

16 Existing Technology of ND Production Detonation Synthesis Preparation of explosive materials mixture containing TNT and RDX Mixture detonation in chambers and obtaining blend containing ND, other carbon structures and metals ND separation and purification by boiling in nitric acid for a long time and washing The product of low quality! ND reactor in Sarov Polluting and Dangerous Technology! 16

17 Ray Techniques Green Technology 1. Preparation of targets from carbon black and hydrocarbon binder 2. Laser treatment of targets in liquid accompanied with ND synthesis and obtaining carbon blend free of metals 3. ND isolation and cleaning by flotation method in deionized water 4. ND surface modification according to customers needs Advantages: 1. Environment-friendly and non-hazardous technology 2. Control ND crystal dimensions 3. Enables monodispersed ND of much higher quality: high purity, metal- and graphite-free high homogeneity of grains, polycrystalline-free controlled surface chemistry lower cost in mass production 4. Fits wider scope of potential applications 5. Allows to achieve better results in High promise for Nanomedicine each application 17

18 Who Says RayND is the Best? The world s leading experts in the field of ND tested RayND and concluded: Prof. Eiji Osawa (Japan): Undisputable advantages of the laser method of producing Nanodiamond by Ray Techniques Ltd in order to turn the modest nanodiamond industry into a major force in nanotechnology, two requirements must to fulfill: one is to start from the purest possible material and to reach the product by clean method; the other is to exclusively work on the primary particles but not on the agglutinates. The first condition is already met by Ray Techniques. (The second one already too) Prof. Vadim Mochalin (USA): NDs produced by Ray Techniques have all advantages of detonation ND powders (small particles size, accessible and tailorable surface, superior mechanical properties, biocompatibility etc.) plus some characteristics that uniquely position them for biomedical applications compared to detonation ND (high purity, control over particle size etc.). Due to these characteristics, the biodegradable polymer composites produced with Ray Techniques NDs will successfully compete on the market with detonation ND. Prof. Oliver Williams (UK): RayND doesn't require any processing to be used. That is a big difference to UDD which has to be bead milled or annealed in hydrogen to make it monodispersed. That's pretty expensive and tedious. 18

19 CARTHER H2020 Project RIA: Carbon nanoparticles for theranostic applications Collaboration with INSA University (Lyon, France) and Aston University (Birmingham, UK) It was confirmed that ND enter into nucleolus It was confirmed that ND is a good contrast agent suitable for several imaging techniques It was found that in some concentration ND without drugs kill cancer cells not impacting healthy tissues 19

20 ND in Novel Approaches in Medicine 1. Theranostic approach is a combination of therapeutic cancer treatment with diagnostics, i.e. tracking drugs in-vivo using PL and magnetism of nanoparticles ND bio-labels incorporated in drugs enable their tracking within the body due to unique diamond features 2. Our proposal: Using biocompatible nanoparticles with unique features enabling to reach inflammation areas where they penetrate cells and kill them under the impact of specific treatment harmless for healthy cells, subsequently leaving the body ND-filled capsules of 100 nm suitable for passive targeting are prepared The capsules pass healthy tissues and stay in the intercellular space of inflammation area Capsule membranes are dissolved and NDs are released and penetrate pathological cells Some kinds of treatment harmless for healthy cells (e.g. ultrasound, electromagnetic treatment) can cause ND reaction resulting in destruction of cells NDs leave the inflammation area and then the body not affecting healthy tissues The process can be controlled using existing in-vivo-imaging instrumentation due to unique ND properties 20

21 Looking for Partners RT is seeking the partners engaged in Nanomedicine research and interested in using ND for their applications. RT can provide the following: Research in the field of ND laser synthesis: influence of synthesis parameters on ND characteristics Development of ND surface modification and producing bright ND dispersions in accordance with project tasks Participation in ND nano-capsule design together with responsible partner Providing the partners with pure homogeneous ND powders and suspensions in accordance with their requirements Characterization & estimation of ND and ND compounds at partners facilities Upgrading ND synthesis and dispersion technology for project goals Contact Olga Levinson 21

22 Welcome to Jerusalem RT Contact Information: Ray Techniques Ltd, The Hebrew University of Jerusalem, P.O.B , Jerusalem, , Israel Tel: Fax: