Transcript What is Cancer… - Division of Physical Sciences

What is Cancer? Cancer is the evolution
of a cell that grows uncontrollably
1
1000
Number of cancer cells
1 million
1 billion
1 trillion
This evolution results from changes in
the cells’ DNA
Like a combination lock, many genes must be affected for
a cell to become cancer…
…but there are many combinations
3 major challenges where
nanotechnology is needed
• Cancer comes from our cells –
domestic terrorist!
• Cancers are different from patient to
patient
• Cancers continue to change as they
grow
Challenge #1: Cancer comes from our
cells – domestic terrorist!
Bacteria & viruses =
easy to spot
Cancer = difficult to detect,
difficult to treat
Challenge #2: Cancers are different
from patient to patient
Each tumor is like a salad from a salad bar
They all have a unique combination of
ingredients (DNA errors)
Challenge #3: Cancers continue to
change as they grow
Tumors are playing the lottery, trying
to get the right combination to be
able to spread (metastasize)
Number of cancer cells
1
1000
1 million
1 billion
1 trillion
If a tumor is detected too late,
it has probably already won
Using the body’s own defenses as an early
warning system – immune monitoring of tumors
Brad Messmer, Thomas Kipps, Dennis Carson
Peptide library on
beads
F
E
F
F
E
B
C
B
B
C
C
B
C
D
A
Cancer
serum
E
E
F
D
D
A
A
D
A
sort
F
red
B
Parts of the tumor are oxygen
deprived and die
E
A
D
C
green
Normal
serum
Tumor-specific Uptake of nanoparticles- Roger Tsien
Minimal cellular
binding/uptake
Live anesthetized mouse 55
min after tail vein injection
protease
Maximal cellular
binding/uptake
Tumor
contrast
~6
Cleavable peptide lights up spontaneous
mammary tumors in MMTV-polyoma middle
T, iNOS -/- mice
Emmi Olson; Dr. Lesley Ellies (UCSD)
Tumor-specific Nanoparticle Agregation
R.Y. Tsien & R. Mattrey (UCSD); P. Daugherty (UCSB)
Small nonsticky nanoparticles
20-200 KDa
Tumorspecific
proteases
Mutually adherent aggregates
Nanoparticles are
actually much smaller
than cells
Nanoparticle smart bombs attack blood vesicles
which nourish metastatic tumors -David Cheresh
αvβ3-positive
αvβ3-negative
Tumor Mass
Nanoparticle Smart Bombs for Metastatic Solid Tumors
-David Cheresh
anb3-Targeting
Ligand
Hood et
al.,
Science
2002
+ +
+ + + +
+ + + +
+ + + +
+ + + +
+ + + +
+
+
+ +
+
+
+
+
Cationic lipid
Nanoparticle targets anb3 and
delivers mutant Raf gene to tumorassociated vessels
After
treatment
Lung
tumor
before
treatment
2 related simple drugs against anb3 in Phase II trials
(Celengtide –Merck Germany brain cancer) and Phase
III trails (Vitaxin MedImmune for melanoma and prostate
cancer)
Liposome Encapsulated Virus particles
Trogler, Mattrey, Kummel
•Phase I: Use emulsion and ultrasonic processing of liposomes to construct micron
size ultrasonic imaging bubbles.
•Phase II: Incorporate adenoviral nanoparticles within nanosized liposome shells for
targeting CLL and lymphatic tumors.
•Phase III: Incorporate surface receptors for tumor-specific targeting on the liposome
mothership surface.
Liposome or
albumin
shell filled with
PFC
vapor and
adenoviral
or nanoparticle
payload with
surface
targeting
receptors
Y
Ultrasound image from the Mattrey
Lab showing vasculature of lung
tumor with PFC filled bubbles.
Vascular used to classify tumors
Cancer cell detector for surgical margins in breast cancer
• A. Kummel, W. Trogler, I. Schuller, S. Esener, , B. Messmer, D. Messmer,
S. Blair, J. Wang-Rodriguez
•Cell array to automate touch prep of surgical margins in breast cancer and to detect changes
in phenotype with disease progression
•Primary detection via size and shape on a-MUC1 coated array
•Secondary phenotyping with quantum dot labeled antibodies
Dielectrophoresis (DEP) Separation in Blood Samples –
Mike Heller
• Top White bacteria
are separated
from red blood
cells by AC
electric fields
applied to
circular
electrodes
• Bottom 2 types of
cells are
separated by AC
electric field
•
Can be enhanced with cancer specific nanoparticle markers.
•
Goal – find rare cancer cells in blood
(Nature Biotechnology Vol. 16, 541546, 1998)