Regular cancer treatment focuses on killing the cancer cells through large doses of medicine, but it also kills other cells in the body and causes significant side effects and potential long-term effects. UCalgary researcher David Cramb – who looks at using nanoparticles to deliver the drugs solely to the tumor in much smaller, more effective quantities shares the potential breakthroughs that can be made possible through nanomedicine both in the treatment and diagnosis of cancer. Watch the full webinar recording: http://www.ucalgary.ca/explore/nanomedicine-new-way-detect-and-treat-cancer

1. Nanomedicine: the new way to
detect and treat cancer?
David Cramb
Professor, Faculty of Science
University of Calgary
April 11, 2017

2. David Cramb
 Professor in UCalgary's
Faculty of Science
 Head of the Department
of Chemistry
 Research interests are in
the application of
nanotechnology to
biomedicine, including
nanotoxicology, cancer,
membrane dynamics,
and pain transduction

3. Preamble
 Making connections between
cancer and nanoscience
 Serendipitous discoveries often
lead to breakthroughs

4. What is cancer?
4
http://www.cancer.org.au/about-cancer/what-
is-cancer/

5. Anatomy of a tumour
5
http://www.peatom.info/salud/117927/limitaciones-de-ciertos-
farmacos-contra-el-cancer/
Tumour grows, builds collagen matrix around itself
and recruits blood vessels for nutrition

6. What is nano?
6
Assembly of materials from atoms and molecules
The nanomaterial produced is 1-500 nm in dimension

7. Nanoparticle size scale
7

8. Tumours and nanoparticles
8
www.crmagazine.org/SiteCollectionImages/angiogenesis.jpg
Nanoparticles escape
the blood stream
through holes in
blood vessels

9. The nanoparticle cocktail
9
Nanoparticle mixture in Different mixture out
Developing tumour

10. Nanoparticle bioavailability
10
60 μm
Blood vessel wall
Needle
500 m
Vessel wall
Injectate
a b
c
Amino-terminated PEG
coated Quantum Dots
(QDs)
Fast adhesion to vessel
walls
Small: DOI 10.1002/smll.201201848 (2013)

11. Smaller is better
-0.001 0.000 0.001 0.002 0.003 0.004 0.005 0.006
0.00
0.01
0.02
0.03
0.04
0.05
PAA Quantum Dots
Polystyrene Spheres
DOPC Liposomes
kfast(s
-1
)
1/r2
(nm-2
)
Negative NPs
Nano-
leaks
R<250 nm
Delivery
rate >
Rate  1/r2 => geometric dependence
11

12. Collagen matrix changes with
tumour age/size
Collagen stain
pink
SHG Image
Collagen green
PNAS vol. 113 no. 9 > E1142–E1151, doi:
10.1073/pnas.1521265113
Cells from a
mouse model
tumour
Collagen density changes
as tumour grows

13. Nanoparticles to test the
cocktail mixture
13
PNAS vol. 113 no. 9 > E1142–E1151, doi:
10.1073/pnas.1521265113
Electron microscope images
Size and charge in water

14. Tumour penetration and
nanoparticle size
14
Orthotopic tumour using
MDA-MB-435 cellsBlood vessel
PNAS vol. 113 no. 9
> E1142–E1151, doi:
10.1073/pnas.1521265113
Nanoparticle penetration into
tumour depends on nanoparticle
size and tumour age

15. Testing pure collagen –
nanoparticles
15
Collagen
Nanoparticle solution
Open the gate to the collagen and observe nanoparticles going in…

16. Water/collagen interface
Some nanoparticle adhere to
the interface

17. Quantitative prediction of
nanoparticle fate
17
ScoreAuNP|Tumour = Σ μi  βi
i represents the factor in question: drug loading capacity; total accumulation;
accumulation rate; tumor penetration depth
rankingImportance multiplier

18. Heat map matrix for
nanoparticles into tumours
18
PNAS vol. 113 no. 9 > E1142–E1151, doi:
10.1073/pnas.1521265113

19. Test the nanoparticles in an
animal model
Compare 15 nm and 100 nm NPs in a diagnostic
blind trial.
15 nm should be about 2x as effective as 100
nm for detecting small tumours.

20. Small nanoparticle accumulates
2x in small tumour
20
PNAS vol. 113 no. 9 > E1142–E1151, doi:
10.1073/pnas.1521265113
A B
C
D
Bright yellow shows nanoparticle location

21. Human

22. Lessons about animal models
22
Extracellular matrix
changes with time
Nanoparticles can detect
this change
Tumour staging in animal
models vs. human

23. Progress for the cocktail
23
Nanoparticle mixture in Different mixture out
Developing tumour

24. Takeaways
24
Tumours develop a changing collagen fortress (matrix) around themselves
This can be exploited for early detection using nanotechnology
Understanding the collagen matrix in animal models will lead to a better
connection between these models and cancer in humans
That connection will lower the cost of cancer treatment

25. Acknowledgements
25
Tina Rinker Research http://www.ucalgary.ca/rinker/
Sarah Childs Research https://research4kids.ucalgary.ca/profiles/sarah-j-childs
Warren Chan Research http://inbs.med.utoronto.ca

26. Thank you
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