Biomedical imaging using nanotechnology

1. NANOTECHNOLOGY IN CANCER DIAGNOSIS
JINO AFFRALD R
M.Sc. Medical Bionanotechnology
Nanoparticles in diagnostics

2. INTRODUCTION
CANCER
It is a term for diseases in which abnormal cells divide
without control and have ability to invade nearby tissues.
Cancer cells can also spread to other parts of the body
through the blood and lymph systems.
Uncontrolled growth of cells results in tumors
• Benign - These are not cancerous.
• Premalignant - A generalized state associated with
significantly increased risk of cancer.
• Malignant – These tumors are cancerous.
Uncontrolled growth of cells almost anywhere in the body
results in Cancer
• Carcinoma – Cancer that begins in a tissue that lines the
inner or outer surfaces of the body.
• Sarcoma – Cancer that arises from transformed cells of
mesenchymal (connective tissue) origin.
• Melanoma – Is a type of skin cancer that develops from
the pigment-producing cells known as melanocytes.
• Lymphoma – A cancer of the lymphatic system.
• Leukemia – A cancer of blood forming tissues, hindering
the bodies ability to fight infection.
TUMOR AND CANCER
• Cancer is a disease in which cells, almost anywhere
in the body, begin to divide uncontrollably.
• A tumor is when this uncontrolled growth occurs in
solid tissue such as an organ, muscle, or bone.
• COLD TUMOR - Lack of T cells infiltrating the tumor
characterizes “non-inflamed”.
vs
• HOT TUMOR - are characterized by the
accumulation of proinflammatory cytokines and T
cell infiltration “inflamed”.

3. NANOTECHNOLOGY
Nanotechnology is a field of research and
innovation concerned with building
'things' - generally, materials and devices -
on the scale of atoms and molecules.
One application of nanotechnology in medicine involves the use of nanoparticles to deliver drugs, heat, light or other
substances to specific types of cells (such as abnormally proliferating cells). This technique reduces damage to non
targeted cells (healthy cells) in the body and helps in earlier detection and cure of disease.
NANOMEDICINE
• Drug delivery
• Imaging
• Sensing
• Blood purification
• Tissue engineering
• Nanobots for cell repair
• Chemotherapy
• Live cell tracking
• MRI contrast agents
• Combat Multiple drug resistance microorganism.

4. NANOTECHNOLOGY IN CANCER
Nanotechnology-based diagnostic methods are being developed as a promising strategy for
real-time, convenient, and cost-effective cancer diagnosis and detection.
THERANOSTICS
NANOTECH
NOLOGY
DIAGNOSIS THERAPY
NANOTHERAPY
Nanotechnology has the potential to increase the selectivity for enhancing the cancer cell death
while minimizing collateral toxicity to non-malignant cells.
TUMOR
DRUG
DELIVERY
ACTIVE
TARGETING
PASSIVE
TARGETING
Active targeting:- involves selective
molecular recognition of antigens,
frequently proteins, that are expressed
on the surfaces of cancer cells in order
to localize NPs to malignant cells.
Passive targeting:- Takes advantage of
the enhanced permeability and
retention (EPR) effect to increase the
concentration of nanoparticles (NPs)
in the tumor.
EPR effect mediated drug delivery
The tumor vasculature is
extremely leaky and not restrictive.
• EPR effect is a concept by which molecules
of certain sizes (typically a nanoparticle)
tend to accumulate in tumor tissue much
more than they do in normal tissues.
Ligand receptor mediated drug delivery
Efficient and site-specific delivery of
therapeutic drugs.
• A variety of ligands have been
investigated including folate, transferrin,
antibodies, peptides and aptamers. e.g.,
to enable imaging and triggered
intracellular drug release.

5. NANOTHERAPY FOR CANCER
DELIVERING CHEMOTHERAPY
Nano systems can deliver
chemotherapeutic agents by
penetrating through physiological
barriers and get access to more
restricted tumors via targeting by
mechanical deformation of particles.
Example: The delivery of paclitaxel
chemotherapeutics using mesoporous
silica nano constructs.
NANO-ENABLED IMMUNO THERAPY
Nanoparticles for delivery of
immunostimulatory or
immunomodulatory molecules in
combination with chemotherapy or
radiotherapy or as adjuvants to other
immunotherapies.
• Standalone nanoparticle vaccines
are also being designed to raise
sufficient T cell response to
eradicate tumors, through co-
delivery of antigen.
DELIVERING GENE THERAPY
Gene silencing therapeutics siRNAs, have
been reported to have significantly extended
half-lives when delivered either encapsulated
or conjugated to the surface of nanoparticles.
HYPERTHERMIA
• Locally injected or systemically
administered nanoparticles.
• That are activated by a extrinsic energy
sources to generate heat.
• In this process the body tissue is exposed
to high temperatures (up to 113°F).
• Very high temperatures are used to kill the
cancer cells and destroy nearby blood
vessels.
This cooks the area that is exposed to the
heat.
The higher the temperature and duration of
exposure, the greater the effect seen within
tissues.

6. NANOTECHNOLOGY IN CANCER DIAGNOSIS NANOTECHNOLOGY IN
CANCER DIAGNOSIS

7. NANOPARTICLE USED IN COMPUTED TOMOGRAPHY
GOLD NANOPARTICLES
• Special attention recently for their use as CT CA.
• High x-ray attenuation.
• Simple surface chemistry.
• Biocompatibility.
• Easy functionalization.
• designed to incorporate other imaging contrast agents
such as rare earth metals and dyes.
• used as X-ray and multimodal contrast agents.
• Key considerations - size, shape, surface
functionalization, composition, circulation time, and
component synergy.
1. The delivery of a CA payload to the site of interest.
2. Nontoxicity.
3. Contrast enhancement in tumor compared to the
surrounding tissue.
BISMUTH SULFIDE NANOPARTICLES
• Bismuth is less toxic and cost effective alternatives to au.
• Treatment of various conditions and diseases.
• Bismuth-based NP contrast agents for CT have several
advantages over conventional iodinated and Au-based NP
contrast agents because of their high atomic number, high
X-ray attenuation , low cost, and low toxicity.
• Bi2S3 is a most promising NP as contrast agents - high
effective nuclear charge, physical density, and electron
density.
• This high density of free electrons increases the
possibilities for Compton scattering.
• USES – X-ray based imaging and radiotherapy.

8. NANOPARTICLE USED IN MAGNETIC RESONANCE IMAGING
Gold Nanoparticles
Interference from higher bone
absorption to lower organs or soft tissue
absorption which would minimize
radiation dose to the patient.
(T2 contrast agent) Negative
THE CONCEPT OF CORE AND SHELL
Gadolinium-based contrast
agents
• They are the current standard
for MRI contrast agents owing
to their high paramagnetism.
• Clinically approved.
• There are multiple reports of
toxicity.
Superparamagnetic iron oxide
nanoparticles
The magnetic moment or susceptibility of
SPION is higher than that of other
paramagnetic substances.
(T1 contrast agent) Positive
CORE-SHELL FASHION
EXAMPLE : STUDY 1 :- Gold
nanorods coated with
Fe3O4 crystals.
• T1 and T2 relaxation was
investigated. T2 relaxivity was
much higher than T1 .
EXAMPLE : STUDY 2 :- Sio2 coated
coated Gold nanoparticles.
• Plasmon Resonance of Gold-
Silica Nanoshells can be Tuned
Throughout Visible and IR
Spectrum.
Two compounds may be combined together to create a heterogenous structure.
A particle created by using a core of iron oxide and a outer shell of gadolinium and
capable of achieving simultaneous T1 and T2 contrast.

9. NANOPARTICLE USED IN ULTRASOUND IMAGING
PHASE-CHANGEABLE PERFLUOROCARBON
NANOPARTICLES
• Used in thyroid cancer.
• Microbubbles - cannot be targeted to
molecular markers expressed in tumor cells
due to their big size, leading to a big
challenge for ultrasound molecular imaging.
• Phase-changeable perfluorocarbon
nanoparticles may resolve the penetrability
limitation of microbubbles and serve as a
promising probe for ultrasound molecular
imaging.
• After injection followed by LIFU irradiation,
ultrasound signal in tumor area was
significantly increased.
MESOPOROUS SILICA NANOCAPSULE
Au nanoparticle coated mesoporous silica
nanocapsule-based enhancement agents can be
used as an inorganic theranostic platform for
contrast-intensified Ultra sound imaging, combined
chemotherapy and efficient high intensity focused
ultrasound tumor ablation.
SUPERHYDROPHOBIC SILICA NANOPARTICLES
• It is a promising nanoscale stable bubble-precursors under ultrasound
stimulation.
• It has been demonstrated that superhydrophobic modifications were
more important than porous structure for trapping the gas nuclei and
serving as bubble-precursors.
• Produce bubbles for at least 30 min upon ultrasound excitation.
• This particle is not only more stable but also showed a lower threshold
for the production of bubbles as ultrasound contrast agents.
• Several merits over traditional perfluorocarbon droplets and typical
mesoporous silica.
• They are much more stable
• Secondly, it is much easier to control their size
• Easy to modify using well-established methods.
• Easier to attach a payload.

10. ROLE OF NANOPARTICLES IN VARIOUS TYPES OF CANCER DIAGNOSIS
Bladder Cancer
Breast Cancer
Colorectal Cancer
Melanoma
Oral and Oropharyngeal
Cancer Pancreatic Cancer
Uterine Cancer
CANCER
Thyroid Cancer
Lung Cancer
Lymphoma
Nanosponges
Quantum dots
Nano-tubes
Nano-wires
Nanoshells
Superparamagnetic
Nanoparticles
Nanodiamonds
Gold Nanoparticles
NANOPARTICLES IN
CANCER DIAGNOSIS
Kidney Cancer

11. NANOPARTICLE BASED DIAGNOSIS IN BLADDER CANCER
It is the fourth most common cancer in men and tenth in women.
Nanotechnology In Photodynamic Diagnosis & Screening:
Fluorescent or photodynamic diagnosis has become one of the
more promising techniques to improve the contemporary white
light microscopy for detection of bladder cancer.
GOLD NANOPARTICLES
• Bladder cancer often produces high levels of
hyaluronidase.
• Urine from bladders with tumors will degrade
hyaluronic acid.
• This result in dispersion of the nanoparticles and
color change easily visible to the naked eye.
• Cationic gold nanoparticles aggregate with
polyanionic hyaluronic acid and lead to a blue color
change.
• Biosensor
IRON NANOPARTICLES FOR MRI CONTRAST TO IMPROVEMENT
DETECTION OF LYMPH NODE METASTASIS
• Nano formulation of contrast agents.
• Paramagnetism.
• These particles are 30–50 nm in diameter.
• Passively penetrate into the normal lymph node.
MRI with ultra-small superparamagnetic particles of iron oxide
can
• significantly improve
- Sensitivity
- Specificity

12. NANOPARTICLE BASED DIAGNOSIS IN LUNG CANCER
Non-small cell lung cancer causes around 80% to 90% of deaths.
The interesting physico-chemical properties in the nanoscale
have generated immense advantages for nanoparticulate
systems for the early detection and active delivery of drugs for
a better Theranostics strategy for lung cancer.
VIRAL NANOPARTICLES
• Viral nanoparticles obtained from viruses and bacteriophages have
gained interest for various biomedical applications such as
1) drug delivery,
2) biosensing,
3) bioimaging,
4) vaccine development
because of its biocompatibility, flexibility in sizes and shapes, and easy
surface modification.
• Genetically modified oncolytic viruses posses great significance
over conventional chemotherapies in the treatment of lung cancer.
• The inability of chemo-drugs to destroy the cancer stem cells is
well compensated by Oncogenic Virus-based gene therapy.
APOFERRITIN
• Apoferritin is the hollow protein nanocage without
the Iron core
1) Self-assembling 24 polypeptide subunits
2) Internal and external diameters of 8 nm and 12 nm.
• This multifunctional apoferritin was used for the
imaging αvβ3 integrin upregulated cancer cells.
CARBON DOT
• Multi-functionalized, carbon dots based nanoagent can be used for
bioimaging as it emitted visible blue photoluminescence when
excited at 360 nm.
• Gene delivery vehicle for multiple siRNAs (EGFR and cyclin B1) in
lung cancer.
• Accumulated in lung cancer cells by receptor mediated endocytosis
in a targeted manner
• Improved gene silencing and anti-cancer efficacy.

13. NANOPARTICLE BASED DIAGNOSIS IN BREAST CANCER
Worldwide, breast cancer remains as one of the most
common cancer diagnosis and cause of cancer related
death among women.
QUANTUM DOTS
1. Lymph node mapping
2. Non-invasive manner and aid subsequent nodal
dissection.
Quicker, easier, and more precise detection and staging of
breast cancer is possible when quantum dots are emitted
in the IR region.
Photostable - They can emit fluorescent light over a long
period of time without a rapid decline in emission.
GADOLINIUM DOPED SPION
• Gd-doped-SPIONs or Gd oxide – MRI.
• polyol chemical approach produce - Gd-doped SPIONs
which have improved the bioimaging of MCF-7 BC cells by
minimizing both T1 and T2 relaxation times in MRI.
SUPERPARAMAGNETIC IRON OXIDE NANOPARTICLES
• NEGATIVE CONTRAST
Recent study:
• Luteinizing hormone releasing hormone functionalized
SPION.
• Receptors are expressed in >50% of breast cancers.
• Small and highly soluble nanoparticles were actively
internalized in vitro by the breast cancer cells after binding
to their receptors.
MRI of breast cancers dissected after 20-hour exposure to
LHRH-conjugated SPIONs showed that these nanoparticles
were able to enhance the negative contrast of the xenografts.

14. NANOPARTICLE BASED DIAGNOSIS IN COLORECTAL CANCER
1.3 million cases, it is the third most frequent cancer in males and females.
QUANTUM DOTS
• Quantum dots based immunohistochemistry and
conventional IHC are qualitatively analyzed.
• The expression level of large external antigen in
tissue samples of Colorectal cancer were studied.
• Compared with conventional IHC, QD-IHC offered
several noticeable advantages for protein marker
quantification.
1. Higher sensitivity
2. Simpler operation
3. Less human interference
4. Increased capability
5. Simultaneous multifactor analysis
lead to more accurate clinical evaluations.
IRON OXIDE NANO CRYSTALS
Iron oxide NPs have the dual ability to act as both magnetic and
photothermal agents and have been approved for human use as MRI
contrast agents. Magnetic nanoparticles coated with antibodies against
carcinoembryonic antigen and studied. The lower limit of detection was
0.21 ng/mL.
PLGA NANOPARTICLES/NANOCELLS
• PLGA-based polymeric oil-core nanocapsules for curcumin delivery.
1. Elevated drug-loading efficiency
2. That the curcumin-loaded ncs are more effective against CT26
3. Leading to apoptosis and blockade of the cell cycle.
Its been reported that the formulated NCs have a better half-life in
blood circulation than that of the non-PEGylated NCs and accumulate in
the subcutaneous CT26 tumors in mice after complete administration.

15. KEY NANOPARTICLE USED IN CANCER DIAGNOSIS
QUANTUM DOTS
• Are semiconductor nanocrystals.
• That emit fluorescence on excitation.
• High brightness.
• Resistant to photo-bleaching.
• Tunable emission spectra.
• Sentinel lymph-node mapping, targeting and
localizing tumors in vivo.
• Signal strength and their simple routine fabrication
protocols and uniform spectral.
• Photostability
GOLD NANOPARTICLES
• Gold nanoparticles tagged to cancer cell surface
markers can be used for targeted cancer therapy.
• Gold nanoparticles functionalized with anti-EGFR
antibodies have been found to facilitate photothermal
destruction of cancerous cells over expressing EGFRs.
• Contrast agents - High aspect ratio and Larger effective
radius are best suited as highly contrast agents for
imaging.
• photo-absorption - Higher aspect ratio and a smaller
effective radius are suitable for photo-absorption.

16. SUMMARY
Cancer and Types Nanotechnology Nano therapy NPs in CT
NPs in MRI NPs in US NPs in different types of cancer Lead players

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18. THANK YOU
JINO AFFRALD R
M.Sc. Medical Bionanotechnology
Nanoparticles in diagnostics