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Innovation and Development of Study Field Nanomaterials at the Technical University of Liberec

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NANODIAMONDS

Applications in Biology and

Nanoscale Medicine

Technical University of Liberec

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Outline

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Alotropic forms of carbon

Diamond powders

Synthesis

Single – Nano Buckydiamond Particles SNBD

The Fundamental Properties and Characteristics

of Nanodiamonds

- Modification

- Bioapplications

4

Carbon is unique in the number and the variety of its allotropes due to its

valency. Well known forms of carbon include diamond and graphite. In

recent decades many more allotropes and forms of carbon have been

discovered such as fullerene graphene of nanotubes. By mixing

diamond and graphite phases by a nanoscale level of structure,

diamond-like carbon material may be created that at the same time is

amorphous, flexible, and yet purely sp3 bonded "diamond".

Alotropic forms and other

types of carbon

H. O. Pierson, Handbook of carbon, graphite, diamond and fullerens, Properties, processing and application, Noyes

Publications, New Jersey 1993

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mixture

Allotropic forms and other

types of carbon

● Structure of diamond and graphite

● Amorphous carbon

● Fullerene

● Carbon nanotube

http://en.wikipedia.org/wiki/Diamond-like_carbon

C. Soldano, A. Mahmood, E. Dujardin, Carbon 48 (2010) 2127-2150

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There are several methods to produce nanoscale diamond particles. The

simplest one is the milling of larger synthetic or natural microdiamonds

and sorting the smaller fraction out by sieving and fractionated

centrifugation.

Synthesis of diamond powders

● Vertical-type beads-milling machine

● Diamond micropowder

A. Krueger, Journal of Materials Chemistry, 18(2008) 1485 – 1792

B. E. Osawa, Nanodiamonds, Applications in Biology and Nanoscale Medicine, Ed. D. Ho, Springer, 2009

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High density material like zirconia is used to give beads

higher momentum,

Beads are suspended in liquid medium to remove heat,

suspension rotation increase the v term of momentum (not

more than 4000 rpm to prevent the graphitization)

Beads are prepared to precisely spherical shape to reduce

the area of collision,

Axial rotation is adopted to obtain shearing collision,

After the process the centrifugal separation of milled

material is used.


- milling

Nanodiamonds, Applications in Biology and Nanoscale Medicine, Ed. D. Ho, Springer, 2009

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In recent years, we are often shown in TV on how

accurate are the missile attacks, which usually end

up with black smoke coming from the

exact target position.

How many people watching TV realize that about half of

smoke is the DIAMOND.


- detonation

Shenderova, O. A. & Gruen, D. M. Ultrananocrystalline Diamond: Synthesis, Properties, and Applications (William

Andrew, 2006).

Nanodiamonds Applications in Biology and Nanoscale Medicine, Ed. D. Ho, Springer, 2009

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In 1963 Ukrainian physicist named Vladimir Danilenko found

that soot from the explosion of well known military explosive

1:1 mixture of TNT – Trinitrotoluene (C7H5N3O6) and

Hexogen (C6H6N6O6) contain nanodiamond in high

concentration.

The greatest importance among the industrial methods of

synthesis of diamond powders have definitely the

detonation technologies

On the history of the discovery of

nanodiamond synthesis

V. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnology 7, (2012) 11–23

Danilenko, V. V. On the history of the discovery of nanodiamond synthesis. Phys. Solid State 46, 595–599 (2004)

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● Detonation synthesis of

nanodiamonds

Detonation nanodiamonds

● Industrial reactor for the

detonation synthesis of

diamond powders

● Detonation nanodiamonds

http://what-is-nanotechnology.com/co.htm

V. V. Danilenko, Synthesizing and sintering of diamond by explosion, Energomizdat, 2003


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The most critical step in production of single-nano buckydiamond SNBD is

the detonation process. After the detonation of explosives in inert medium,

invisibly small diamond crystals will start to grow from deposition of

unoxidized carbon atoms from the explosive molecules in the thin high-

pressure high-temperature zone, formed behind the rapidly propagating

front of shock wave. It seems that a very large number of crystallization

nuclei simultaneously start the diamond growth process under abundant

supply of carbon atoms generated from incomplete combustion of the

explosives

The crystal growth is suddenly and all at once suspended as the shock

wave passes at supersonic speed from the diamond growth area.

Detonation nanodiamonds

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Structure of detonation nanodiamonds

● A possible structure model for diamond

agglomerates in detonation diamond

● Structure of a single nanodiamond particle

In the certain stage of the detonation synthesis, further drop of the pressure

and temperature drives the P-T parameters to the region where the diamond

is thermodynamically unstable, and this is the reason that detonation carbon

is a mixture of sp2 (graphite) and sp3 (diamond) hybridized carbon atoms.

V. Mochalin, O. Shenderova, D. Ho, Y. Gogotsi, Nature Nanotechnology 7, (2012) 11–23

A. Krueger, Journal of Materials Chemistry, 18(2008) 1485 – 1792

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oxygen termination hydrogen termination

Surface of nanodiamonds

P. Niedzielski, Wytwarzanie i zastosowanie proszków diamentowych, Wydawnictwo Politechniki Łódzkiej, Łódź, 2011

The surface of nanodiamonds is full of free (dangling) bonds, that

chemically bind to the atoms of the environment (usually oxygen and

hydrogen). This phenomenon called „termination” strongly affects the

physicochemical properties of nanodiamond particles.

● Bonds on the surface of diamond

Terminated surface of

nanodiamonds should be

considered as perfect

starting material for further

chemical of biological

modifications.

14 Nanodiamonds Applications in Biology and Nanoscale Medicine, Ed. D. Ho, Springer, 2009

It has been proposed that DND may

be applied for medical purposes,

either alone or biofunctionalized, in

diverse medical fields, including

oncology, cardiology, gastroenterology

and dermatology. DND conjugates are

chemically stable and do not alter the

activity of bound biomolecules.

After the synthesis and purification the surface of nanodiamond particles

contains a complex array of surface groups, including carboxylic acids,

esters, ethers, lactones, amines, etc.

Surface of nanodiamonds

● Schematic of possible surface

functionalization of nanodiamonds

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The suspension of nanodiamond particles introduced into a tumor cell

culture led to their aggregation and in a consequence by damaging the cell

membrane resulted in their death.

A.P.Puzyr, D.A.Neshumayev, V.S.Bondar V.Yu.Dolmatov, I.V.Shugalei, N.P.Dubyago, S.V.Tarskikh, G.V.Makarskaya: the

influence of detonation nanodiamond powder on blood cells: . Lee and N. Novikov (eds.), Innovative Superhard Materials

and Sustainable Coatings for Advanced Manufacturing, 155–167. 2005 Springer. Printed in the Netherlands

● Aggregation of tumour cells

● Destroyed tumour cells

Properties of nanodiamonds

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Depending on size of nanodiamond particles and aggregates

the possible areas of their application differ from each other.

● Schematics of the size ranges of DNDD primary particles and aggregates in

relation to different possible areas of biomedical and healthcare application

Size vs. destiny


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Applications of nanodiamonds

- Seeding of CVD Diamond Films

As a seed material for CVD diamond

growth, nanodiamond particles play an

important role for the development of

medical implants. Seeding with DND

allows obtaining coatings with small grain

size and, therefore smooth surface that are

important for medical implant applications.


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0

2

4

6

8

10

12

14

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Day 0 Day 1 Day 2 Day 3

Days

Ear

Sw

elling

(mm

x 1

0 -

2)

DNFB negative control

DNFB positive control

DETONATION Ear only

DETONATION Ear +Abdomen

The application of diamond powders in pharmaceutical – cosmetological

industry is related to their properties such as: bactericidal activity, inhibition

of the oxidative stress, anti-allegric and anti-inflamatory activity.

M. Batory, D. Batory, J. Grabarczyk, W. Kaczorowski, B. Kupcewicz, K. Mitura, T. H. Nasti, N. Yusuf, P. Niedzielski, Journal of

Nanoscience and Nanotechnology Vol. 12, 1–10, 2012

● Allergy tests results of nanodiamond powder

based cosmetic formula


– health care products

The study shows that diamond

powder particles do not cause

allergies. All obtained results of

ears swelling are below 4 ×10−2

mm, which is the limit value

assumed in the clinical

examinations.

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The diamond powder is strongly hydrophilic. It retains water and binds it

to the surface of the skin thus it slows the transepidermal water loss

(TEWL) and influence the function of the hydro-lipid skin coat.



The structures of oily and acne complexion of patient’s chick before

and after the application of the cream with detonation powder.

● Before

● After 2 weeks

● After 4 weeks

M. Batory, D. Batory, J. Grabarczyk, W. Kaczorowski, B. Kupcewicz, K. Mitura, T. H. Nasti, N. Yusuf, P. Niedzielski, Journal of

Nanoscience and Nanotechnology Vol. 12, 1–10, 2012

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Nanodiamonds are also considered for cosmetics and health care

applications due to their ability to bond with biological materials, improve

durability and robustness of a composition. Provide protection against

harmful UV light.

P. Niedzielski, Wytwarzanie i zastosowanie proszków diamentowych, Wydawnictwo Politechniki Łódzkiej, Łódź, 2011

● Examples of cream bases

prepared using nanodiamonds

● Example of the pattern for the

commercial product



21 R.A.Shimkunas, E.Robinson, R.Lam, S.Lu, X.Xu, X.Q.Zhang, H.Huang, E.Osawa, D.Ho: Nanodiamond–insulin

complexes as pH-dependent protein delivery vehicles, Biomaterials 30 (2009) 5720–5728

Nanodiamond Insulin


– insulin carriers

According to research carried out by a North Western University team in the

US, nanodiamonds were found to have a very important medical use when

they loaded with insulin and placed around open wounds.

Insulin encourages skin cells to

proliferate and divide, restores

blood flow to the wound and

suppresses inflammation and fights

infection.

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– films in drug delivery

Zhu Y, Li J, Li W, Zhang Y, Yang X, Chen N, Sun Y, Zhao Y, Fan C, Huang Q. Theranostics 2012; 2(3):302-312

A ND-drug film can be implanted

immediately after surgical removal of a

tumour to target residual cancerous cells

so as to effectively prevent the tumour

from recurring. In addition, a ND-drug

film can be more applicable to the

treatment of superficial tumours such as

breast cancer, head and neck cancer,

and skin cancer, or superficial skin

inflammations, wherein the drug is

delivered transdermally to tumours or

inflammation sites, reducing the toxicity

on normal tissues. ● Nanodiamond drug-funtionalized film

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– clusters in drug delivery

Zhu Y, Li J, Li W, Zhang Y, Yang X, Chen N, Sun Y, Zhao Y, Fan C, Huang Q. Theranostics 2012; 2(3):302-312

The investigation of the assembly

principles and characteristics of

different functional molecules on NDs

would help to establish the models and

theories for building ND-based

versatile drug delivery systems, which

would serve as the basis for

developing a variety of ND-based drug

delivery systems with high efficiency

and low toxicity to prevent and/or treat

various cancers.

● Schematic illustration showing the different

loading of different functional molecules on NDs

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Applications of nanodiamonds –

gene delivery

● Example of the attachment of specific DNA

to the nanodiamond surface for gene delivery

to cells / tissues using DNA plasmids.

● Example how nanodiamonds carrying a toxic

drug or gene-regulating microRNA are taken up by

a cell and how the attached “drug” may be released

for a specific treatment.

X. Zhang, M. Chen, R. Lam, X. Xu, E. Osawa, D. Ho, ACS. Nano, 2009, 3, 26092616

http://boards.medscape.com/forums/?128@@.2a36aa4d!comment=1&cat=All

25 V. Mochalin, Y. Gogotsi, J. Am. Chem. Soc., 2009, 131 (13), pp 4594–4595

The ODA-modified (octadecylamine) nanodiamond is highly fluorescent.

The intensity is so high that a bright blue fluorescence can be easily

detected with the bare eye at diamond concentrations as low as 0.004 %

by weight. Though the fluorescence mechanism requires further studies,

the ODA-functionalized nanodiamond can now be used in many

applications where visual detection of nanoparticles is required, such as

biomedical imaging and drug delivery systems.

● Bright blue fluorescence of the octadecylamine-modified nanodiamond

Fluorescent nanodiamonds as

cellular biomarkers

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Nanodiamonds emit bright fluorescence at 550-800 nm from nitrogen-

vacancy-centres produced by high-energy ion beam irradiation and

subsequent thermal annealing. The emission, together with

noncytotoxicity and easiness of surface functionalization, makes nano-

sized diamonds a promising fluorescent probe for single-particle tracking

in heterogeneous environments.

Fluorescent nanodiamonds as

cellular biomarkers

Proc Natl Acad Sci U S A. 2007 January 16; 104(3): 727–732

http://awsch-web.physics.ucsb.edu/research/solid_state/nitrogen_vacancy/index.php

● Observation of single FNDs in a HeLa cell.

● Schematic of Nitrogen Vacancy Centre

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Utilizing the inherent surface chemistry of

detonation nanodiamonds, an amine-

functionalized Gd(III) complex was

covalently bound allowing visualization of

nanodiamond particles by MR imaging. The

relaxivity of the Gd(III) contrast agent

increased nearly 10-fold in comparison to

the free agent upon conjugation to the

nanodiamond platform. Numbers 4 and 5

denote samples with the highest Gd(III)

concentration


– Magnetic Resonance imaging

● MR images of

nanodiamond samples.

L. Manus, D. Mastarone, E. Waters, X. Zhang, E. Schult-Sikma, K. MacRenaris, D. Ho, T. Meade, Nano Lett. 10 (2010)

484–489.

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