1. Visualization of Breast Cancer for Diagnosis using Nanoparticles
Ye-Eun Kang
Functional Soft Nanomaterials Lab.
Supervised by Prof. Seung Yun Yang

2. Breast Cancer  Early diagnosis is very important! Breast Cancer
- Cancer that develops from breast tissue
- Most commonly develops in cells from the lining of milk ducts and
the lobules that supply the ducts with milk
- Risk factors
: Being female, obesity, lack of physical exercise, drinking alcohol, older age, family history, etc.
Incidence Rate
Mortality Rate
Survival Rate(2001~2012 수술환자 대상)
한국유방암학회 2016
중앙암등록본부 2016
통계청 2016
If detected early, breast cancer is curable
 Early diagnosis is very important!

3. Diagnosis methods for breast cancer
Breast Self Examination
- Anyone can do it easily at no cost
Radiological diagnosis
- Use electromagnetic wave and ultrasonic wave to generate images
- Mammography, CT scan, MRI scan, and ultrasonography CT
cancer
MRI
cancer
normal
PCR (Polymerase Chain Reaction)
- Amplify certain regions of DNA using polymerase chain reaction
- Be used for DNA sequencing, analyzing the functionality of genes, and diagnosing hereditary cases of breast cancer
Immunochemistry
- A method by which cancer cells are detected in the body by antigen-antibody reaction
- Staining technique used to identify cancer cells in a tissue sample

4. Biomarker-specific ligand
Materials for breast cancer diagnosis
Materials for breast cancer diagnosis
Concept
Biomarker
An indicator that can detect changes in the body (health or disease state) by using proteins, DNA, RNA, and metabolites
Substances that are specifically expressed in breast cancer cells
Gene (BRCA1/2, PALB2, BRIP1)
Receptor (HER2, ER, PR)
MicroRNA (Let-7a, MiR-21)
Biomarker-specific ligand
A substance that specifically binds to a biomarker
Allow drugs or imaging agents to specifically target breast cancer
Antibodies, nucleic acid, peptides that complementary bind to breast cancer biomarkers
Imaging agent
Material that visualizes the size (volume) and location of breast cancer cell (tissue)
Allows to monitor the diagnosis or progress of the cancer
Contrast agent (Iodine ion compound, gadolinium ion compound)
Fluorescent substance (Fluorescein)

5. Fluorescent substance
Imaging agent for breast cancer diagnosis
Conventional imaging agent for diagnosis
Contrast agent
Fluorescent substance
- A substance that increases the contrast of tissue to more accurately distinguish normal and lesion tissues
- Through oral or intravenous administration
Ex. Iodine ion compound – for CT scan
Gadolinium ion compound – for MRI scan
- A substance that can re-emit light upon light excitation(UV or visible light)
- Used to label and track cells in fluorescence microscopy applications
Ex. Fluorescein(green) and its derivatives CT
MRI
breast cancer cell(green), estrogen receptor α(red)
- non-contrast
+ contrast
normal blood vessels
brain tumor
 When used in vivo, it can sometimes cause side effects
 Fluorescence intensity decreases with time (photobleaching)
 Exhibit narrow absorption spectra and broad emission spectra
 Can cause side effects such as vomiting, anaphylactoid reaction, and, in the worst case, death
 Short imaging time
T. Fehm et al., Breast cancer research, 10, R76 (2008)

6. Nanoparticles as imaging agents for breast cancer diagnosis

7. Nanoparticles enable efficient and accurate diagnosis
Why are nanoparticles used as imaging agent
for breast cancer diagnosis?
Nanoparticles
- Nano-scaled(1 – 100 nm) materials
 unique interaction with biological systems at molecular level
- Have a very large surface area relative to their volume
 have various physicochemical properties
(such as strength, conductivity, catalytic activity, optical properties, magnetic properties, etc.)  various molecules can attached to the nanoparticle surface (targeting ligands – peptide, nucleotide, antibody, etc.)
Nanoparticles enable efficient and accurate diagnosis

8. Fluorescent substance
Nanoparticles for breast cancer diagnosis
Contrast agent
Gold nanoparticles (AuNPs) for CT scan
Superparamagnetic iron oxide nanoparticles (SPIONs) for MRI scan
Fluorescent substance
Quantum dots (QDs) for in-vivo, in-vitro bioimaging

9. Gold nanoparticles for CT contrast agents
Gold nanoparticles (AuNPs)
- Unique electronic, magnetic, optical and catalytic properties
 tunable by changing the size, shape, surface chemistry, or aggregation state.
- Have biocompatibility (bio-inert)
- Gold absorb more X-ray energy than iodine
 gold-based CT agents can show high-resolution image than conventional iodine-based CT agents

10. Gold nanoparticles for CT contrast agents
aorta
Hematoma region
before
5 min
1 h
2 h
4 h
12 h
After 24 h of incubation

11. Superparamagnetic iron oxide nanoparticles for MRI contrast agents
Superparamagnetic iron oxide nanoparticles (SPIONs)
- Has magnetic properties only in the presence of an external magnetic field.

12. Superparamagnetic iron oxide nanoparticles for MRI contrast agents

13. Quantum dots for visualization of cancer cell
Quantum dots (QDs)
- Semiconductor fluorescent nanoparticles
- Have photo-stability  emit fluorescent light over a long time without photobleaching
- Emission spectrum, fluorescence property depends on size
- Exhibit broad absorption spectra and narrow emission spectra
 possible to label multiple molecular targets simultaneously
Quantum size effect
Quantum dots for in-vivo cancer targeting and imaging

14. Quantum dots for visualization of cancer cell
In vitro
In vivo
0.6 nmol 6 h circulatin
0.6 nmol 24 h circulatin
0.4 nmol 2 h circulatin
0.4 nmol 2 h circulatin

15. Quantum dots for visualization of cancer cell
In vivo
0.6 nmol 6 h circulatin
0.6 nmol 24 h circulatin
0.4 nmol 2 h circulatin

16. Conclusion
Early diagnosis is important because breast cancer can be treated at early detection
Conventional imaging agents for breast cancer diagnosis can cause side effects and are relatively inefficient
Nanoparticles have been developed as imaging agents that overcome the drawbacks of conventional imaging agents for breast cancer diagnosis

17. Thank you