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Nanotechnology: The ultimate tools for medicine ?. PD Dr.med Patrick Hunziker Patrick.Hunziker@unibas.ch Div. of Intensive Care Medicine & Cardiology Physics in Medicine Research Group University Hospital Basel. What happened to the Bayer shares ?. Eric Drexler, 1986.

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nanotechnology the ultimate tools for medicine

Nanotechnology:The ultimate tools for medicine ?

PD Dr.med Patrick Hunziker

Patrick.Hunziker@unibas.ch

Div. of Intensive Care Medicine & Cardiology

Physics in Medicine Research Group

University Hospital Basel

current impact of nanotech on medicine
Current impact of nanotech on medicine:

Medline impact:

117 / 11’000’000 citations with “nanotechnology”

(mostly “science fiction” articles)

compare:

120’000 citations with “catheter”

=> in medicine, nanotechnology is in its infancy !

dimensions of life dimensions of medicine

treatment

in vivo diagnosis

body

human eye

stethoscope

artificial hips

organs

X-ray

therapeutic radiation

MRI

scalpel

ultrasound

blood

vessels

catheters

catheters

neurons

most

cells

nucleus

cell

organelles

supramol.

assemblies

proteins

small molecules

atoms

dimensions of life - dimensions of medicine

body components

m

m

dm

dm

cm

cm

mm

mm

( only blood cells:microscopes )

mm

mm

biochemical tests

nm

nm

drugs

“there is plenty of room at the bottom”

medical treatment today a fundamental size mismatch

body

artificial hips

organs

therapeutic radiation

scalpel

blood

vessels

catheters

neurons

most

cells

disease

starts here

your doctor’s watchmaker tool

nucleus

cell

organelles

supramol.

assemblies

your doctor is watering flowers..

proteins

small molecules

atoms

Medical treatment today: a fundamental size mismatch...

body components

m

m

dm

dm

cm

cm

mm

mm

mm

mm

nm

nm

drugs

where all the action is the cell

vesicles

nucleus: genome,

gene expression

channels

endoplasmatic

reticulum

fibrils

receptors

mRNA

mitochondria

ribosomes

membrane proteins

proteins

Where all the action is: the cell !

cytoplasm:

metabolism

watering flowers or flooding the neighburhood treating atherosclerosis with lipid lowering drugs

some lipid lowering drugs:

effects on plaques

can save lifes

effects on liver

muscles:

can lead to cell death

can endanger human life

can endanger large companies

effects on

immune system

Watering flowers or flooding the neighburhood ?treating atherosclerosis with lipid lowering drugs

arteriosclerosis:

- begins at the cell

-> focal lesions in the arteries

- leads to myocardial infarction and stroke

arterial plaque

using a bulldozer for watchmaking the example of coronary artery disease

Cells begin to accumulate cholesterol

altered micromechanics

inflammation of the arteriosclerotic plaque

vessel narrowing

heat

reactive molecules

cytokines

altered membrane protein

expression

plaque rupture

angina

stroke

myocardial infarction

Using a bulldozer for watchmaking ?the example of coronary artery disease
watering flowers or flooding the neighburhood treatment of cancer

anti-cancer drugs:

typically kill rapidly growing cells

kill rapidly growing

cancer cells

may save human lifes

kill normal, rapidly growing cells

-intestine -> vomiting

-blood cells -> anemia

-immune system ->infections

may endanger life

may not kill

slowly growing cancer cells

cancer may recur

Watering flowers or flooding the neighburhood ?Treatment of cancer

cancer:

- starts as a single cell

-is a focal disease

medical diagnosis treatment tomorrow improve current technology

body

m

Better materials for prostheses, stents etc:

strenght, durability, biocompatibility

organs

dm

cm

blood

vessels

Enlarge catheter-based measurement toolbox

mm

neurons

most

cells

nucleus

cell

organelles

mm

supramol.

assemblies

Biochemical tests: more sensitive/specific

faster

bedside/point of care

array of parameters

less expensive

proteins

small molecules

nm

atoms

Medical diagnosis & treatment tomorrow: improve current technology
medical diagnosis tomorrow break completely new ground

body

m

organs

dm

cm

blood

vessels

mm

in vivo small scale disease characterisation

neurons

most

cells

in vivo single cell probes

nucleus

in vivo cell nucleus probes

cell

organelles

mm

in vivo probes for cell organelles

supramol.

assemblies

in vivo probing of fibrous structures

in vivo membrane protein monitoring

proteins

in vivo biochemical monitoring

small molecules

nm

atoms

Medical diagnosis tomorrow:break completely new ground !
medical treatment tomorrow break completely new ground

body

m

organs

dm

- to specific locations

- to specific tissues

- to specific cells

- based on sensor information

cm

blood

vessels

mm

neurons

most

cells

nucleus

cell

organelles

mm

supramol.

assemblies

proteins

small molecules

nm

atoms

Medical treatment tomorrow:break completely new ground !

-targeted drug delivery

-nanomechanical interventions

e.g. - kill cancer cells directly

- repair cellular substrate of

atherosclerosis early

- find/treat infections locally

- directed somatic gene therapy

- attack Alzheimer’s disease

point of care diagnosis immunological array testing
Point of care diagnosis:immunological array testing

micromosaic immunoassays applied to clinical inflammation markers

10mm

M.Wolf, Kantonsspital Basel/IBM Rüschlikon8/01

Bernard, Michel & al, IBM Rüschlikon 8/01

point of care diagnosis nanomechanical olfactory sensors
Point of care diagnosis:nanomechanical olfactory sensors

Baller, Lang, Gerber & al, IBM /Uni Basel

Arntz, IBM /Uni Basel /Kantonsspital Basel

nanotechnology in action observing disease processes involving fibrils
Nanotechnology in action: observing disease processes involving fibrils

growth of beta-amyloid (->Alzheimer !) visualized by AFM

C. Goldsbury, J. Kistler, U. Aebi et al, J. Mol. Biol.285, 33 (1999)

gene chips a promizing target for nanotech
Gene chips: a promizing target for nanotech

The human genome project:

man>: ~ 40’000 genes

-> measure activation of each (mRNA)

-> no more than 40’000 enzymes

-> all biologically relevant substance are substrates of these enzymes measurable

www.clontech.com

a gene microarray featuring

8000 individual human cDNAs

drug delivery devices

site-specific drug application

- e.g. selectively targeting cancer cells with anticancer drugs

Drug delivery devices

Sensor driven drug application

- e.g. insulin treatment in diabetics

single cell needles syringes

drug delivery device

“closed loop therapy”

nondestructive monitoring

of cell metabolism

cell gene therapy

based on sensor info

Single cell needles/syringes
nanotubes in medicine
Nanotubes in Medicine

Erased due to publication restrictions of novel technology

topics for nanomaterials in medicine
Topics for nanomaterials in medicine

Biocompatibility

Fundamentals of self-assembly

Improved mechanical characteristics

Drug releasing materials

Biodegradable materials

the single cell as treatment target learn from creation

virus specific

protein

T

Lymphocyte

cell specific

surface molecules

“lethal kiss”

The single cell as treatment target:Learn from creation !

nucleus

steps toward single cell treatment

nucleus

virus specific

protein

catheter

sensor

unit

cell specific

surface molecules

wiring

effector

unit

Steps toward single cell treatment
steps toward single cell treatment1

Heat production

nucleus

virus specific

protein

anaerobic metabolism

lactate production

pH decrease

sensor

unit

cell specific

surface molecules

power,

logic

effector

unit

Steps toward single cell treatment

Nano-Robot

biologic examples for simple autonomous units

self replication

mobility

protein synthesis

gas transport

pH buffer

glycolysis

red blood cells:

shape change,

degranulate

aggregate

upon signal

blood platelet:

self replication

protein synthesis

glycolysis

metabolism

mobility

self replication

virus:

“cristal” with software

can dock to/invade cells.

none

neurons:

electrical response to

electrical/chemical stimuli

complex

Lymphocytes:

recognize self and non-self

specific response

complex

Biologic examples for simple autonomous units

key capability

energy production

not capable of

wishlist for single cell sensors in the nanoscale
Wishlist for single cell sensorsin the nanoscale

electric potential

heat production

pH

Redox potential

gas pressures

NO concentration

concentration of small biomolecules (lactate, cations, cAMP..)

presence/concentration of proteins

presence of mRNA

Receptor binding phenomena

tip-based spectroscopy (optical, NMR)

potential problems of nanotechnology in medicine
potential problems of nanotechnology in medicine

Number of cells in the body ~1012

-> for biological impact: treat >108 cells

=> new manufacturing methods needed

Will the immune system recognize and eliminate nanoparticles ?

(immune response, biocompatibility, nano-mimickry)

Influenza viruses kills 10 Mio people during world war I

Computer virus shoots down millions of PC’s worldwide in y 2000

-> Autonomous, self-replicating nano-agents:

a danger for the future ?

nanoviruses
Nanoviruses

“A synthetic nanovirus

is 5 years away”

C.Hutchinson, AAAS 2001

BBC News

foresight guidelines on molecular nanotechnology
Foresight Guidelines on Molecular Nanotechnology

Version 3.7: June 4, 2000

MNT (molecular nanotechnology) device designs should incorporate provisions for built-in safety mechanisms, such as:

1) absolute dependence on a single artificial fuel source or artificial "vitamins" that don't exist in any natural environment;

2) making devices that are dependent on broadcast transmissions for replication or in some cases operation;

3) routing control signal paths throughout a device, so that subassemblies do not function independently;

4) programming termination dates into devices, and

5) other innovations in laboratory or device safety technology developed specifically to address the potential dangers of MNT. Further research is needed on MNT risk management, as well as the theory, mechanisms, and experimental designs for built-in safeguard systems.

ecophagy
Ecophagy

Some Limits to Global Ecophagyby Biovorous Nanoreplicators,with Public Policy Recommendations

Robert A. Freitas Jr.

http://www.foresight.org/NanoRev/

“Replication time t of biovorous nanoreplicators is limited by substrate availability: t >12’000 sec.”

“Early detection is key to effective defense”

nanotech in medicine ethical questions
Nanotech in Medicine:Ethical Questions

Gradual improvement of current tools/techniques

-> probably acceptable to everybody

-> which parts of mankind will profit ?

Breaking new ground:

Creation of autonomous (“living”) agents

Blurring of frontiers between “beings” and “things”

-> “allowed to mankind” ?

-> “acceptable to society” ?

-> controllable at long term ?

-> potential for infectious spread of self-replicating machines ?

nanotech in medicine outlook
Nanotech in Medicine:Outlook

1) Nanotechnology will

-revolutionize medical laboratory diagnosis within a few years

2) Nanotechnology will break new ground in

- monitoring technology in critically ill patients

- in vivo diagnosis within the body

- allowing single cell diagnostics, monitoring & treatment in the body

- will outperform the impact of gene therapy

3) Nanotechnology will

- produce simple prototypes of nanorobots within a decade, thus

- blur the frontier between “beings” and “things”

-> an array of ethical question will be raised -> to be addressed early

thanks to
Thanks to

The physicists for inventing nanotech

Everybody in the Nano NCCR, esp Prof. Guentherodt

for their great collaboration with that strange species

of “medical doctor interested in physics”

Prof. Pfisterer and Prof. Marsch

for encouragement & support

My wife and children for the lonely hours

due to nanomedicine