The Case of Carbon Nanotubes Professor Kostas Kostarelos - - PDF document

the case of carbon nanotubes
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The Case of Carbon Nanotubes Professor Kostas Kostarelos - - PDF document

Engineering the Pharmacology & Toxicology of Nanomaterials The Case of Carbon Nanotubes Professor Kostas Kostarelos Nanomedicine Lab Centre for Drug Delivery Research The School of Pharmacy, University of London Carbon Nanotubes: S tuff


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SLIDE 1

University of Tokyo, October 2010

Engineering the Pharmacology & Toxicology of Nanomaterials

The Case of Carbon Nanotubes

Professor Kostas Kostarelos

Nanomedicine Lab Centre for Drug Delivery Research The School of Pharmacy, University of London

Ballistic transport means that electrons in t b t l h f t th i Six times lighter than steel but more than 500 times stronger.

Carbon Nanotubes: S tuff of Dreams?

nanotubes travel much faster than in metals, and they don't dissipate. This conductivity could be useful in making electric paint, absorbing static, storing energy or replacing chips' silicon circuits. The best material ever discovered for moving heat from one place to another, nanotubes are potentially handy for cooling confined spaces like PCs. Because they emit light, nanotubes could be used in optical fiber. Nanotubes can be bent 120 degrees and snap back. Potential failure is therefore reduced. Strong covalent bonds mean that if an atom goes missing, the remaining carbon atoms will fill the gap. Unlike silicon circuits, which need to be "drawn," nanotubes form on their

  • wn in the presence of a catalyst.

Almost chemically inert, nanotubes won't prompt reactions in other

  • materials. That quality is potentially

useful in atomic microscopes or for drug delivery.

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SLIDE 2

University of Tokyo, October 2010

Carbon Nanotubes: S tuff from Hell?

Amorphous carbon Graphite Diamond

Carbon Nanotube Definition

from Amorphus Carbon to Novel Nanomaterial

Amorphous carbon Graphite Diamond Fullerene Carbon nanotube

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SLIDE 3

University of Tokyo, October 2010

Carbon Nanotubes in Biology & Medicine

  • Only a few types of CNT used in

biomedical applications biomedical applications

  • Pristine material without surface

modification should be avoided

  • The fundamental needs to be

achieved are: ‐ aqueous and biological fluid dispersibility ‐ nanotube individualisation

Kostarelos, Bianco, Prato. Nature Nanotechnology, 2009

Universality in f‐CNT intracellular uptake?

Kostarelos et al., Nature Nanotechnology, 2007, 2, 108‐1484

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SLIDE 4

University of Tokyo, October 2010

CELL MEDIUM

The ‘Nanoneedle’ Hypothesis

CYTOPLASM

Pantarotto et al. Angewandte Chemie International Edition, 2004 Lacerda et al. Journal of Materials Chemistry, 2008 Lacerda et al. NanoToday, 2008

Carbon Nanotubes for Biomedicine

Why is all this interesting? Why is all this interesting?

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SLIDE 5

University of Tokyo, October 2010

CNT‐mediated siRNA delivery

HeLa 3 hrs transfection siRNA ‐ ATTO 655

Liposome:siRNA f‐CNT:siRNA

nuclei siRNA DIC

Evaluate

Intracellular Fluorescence (siRNA)

48 hr

Al‐Jamal, K. et al., FASEB J, 2010

Carbon Nanotube Pharmacology Pharmacology

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SLIDE 6

University of Tokyo, October 2010

What’s ‘ Good’ and what’s ‘ Bad’

CNT Pharmacology

  • ‘ Good’ is long blood

circulation & high degree of excretion ‘ d’ l

  • ‘ Bad’ is tissue accumulation

that may lead to side effects

Radiolabelling

Intravenous (tail vein) MWNT DTP A[ 111I ]

Administration CNT Pharmacology

N N N O O O

N O O N H O N CO2H N HO2C N CO2H CO2H N O O NH

Mice / Rats

MWNT-DTP A[ 111In]

(50 µg / 1.5-10 MBq)

[111In]DTPA

In O O O O O O

=

S PECT/ CT imaging

Evaluate

Mice / Rats 5min, 30 min, 24 hr

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SLIDE 7

University of Tokyo, October 2010

100 Standard Head

Tissue Distribution (Dynamic 1-D S

PECT)

CNT Pharmacology

  • activity Level (a.u.)

Standard Heart Kidneys

N O O NH

Real time: 5 min

Radio Bladder Tail

Lacerda et al, Advanced Materials, 2008

(TEM analysis of urine)

Urinary Excretion

CNT Pharmacology

SWNT-[DTPA]

(scale 500 nm)

MWNT-[DTPA]

(scale 100 nm) Singh et al, PNAS, 2006

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SLIDE 8

University of Tokyo, October 2010

Bundled MWNT found in the glomerular capillaries

(kidney TEM)

Urinary Excretion Mechanism

CNT Pharmacology

500 nm

Individual CNT

(kidney TEM)

Urinary Excretion Mechanism

CNT Pharmacology

Lumen of glomerular capillary Lumen of glomerular capillary E E P EC RBC Urinary space 0.5 μm Urinary space E P 0.2 μm BM E

30 min 5 min

Lacerda et al, SMALL, 2008

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SLIDE 9

University of Tokyo, October 2010

Carbon Nanotube Toxicology Toxicology

CNT Toxicology

Peritoneal Model CNT Toxicity

  • Surfactant‐based dispersions of

pristine, long (>20µm) CNT

  • d

b fib

Kostarelos, Nature Biotechnology, 2008

  • Compared to asbestos fibers
  • Reported asbestos‐like reactivity

that can lead to carcinogenicity

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SLIDE 10

University of Tokyo, October 2010

Conclusions

CNT Pharmacology & Toxicology

  • CNT interact with biological matter leading to

biological activity

  • CNT structural and surface characteristics

determine biological profiles in vitro and in vivo

  • Chemical functionalisation with small

hydrophilic groups that can lead to individualised CNT can cross the glomerular filter and be excreted in urine h l d h h

Kostarelos, Nature Biotechnology, 2008

  • Processes that can lead to shorter that 5µm

CNT can completely alleviate the asbestos‐like reactivity

  • CNT Structure‐Biological Function studies are

the only way forward

Carbon Nanotubes in Medicine

into perspective into perspective…

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SLIDE 11

University of Tokyo, October 2010

Carbon Nanotubes in Medicine

(preclinical animal models only)

  • Oncology is the prime indication

when CNT are used in medicine when CNT are used in medicine

  • Proof‐of‐principle systemic

targeting of CNT (both coated and functionalised) using peptides (RGD) and antibodies shown

  • Only two studies reported

y p therapeutic efficacy to prolong survival of tumor‐bearing animals

  • Disease models in immunology and

neurology at the proof‐of‐principle

Kostarelos et al. Nature Nanotechnology, 2009

The Funding

NINIVE