1. NANOMEDICINE
“ Tiny ” brings a plethora for
life
PREETHI SRIDHARAN
IV M.Sc. (BIOTECHNOLOGY)
ANNAMALAI UNIVERSITY
ANNAMALAI NAGAR

2. NANOMEDICINE
 The science and technology of diagnosing,
treating and preventing disease and traumatic
injury, of relieving pain and of preserving and
improving human health, using molecular
tools and molecular knowledge of the human
body.

3. Applications of nanotechnology :

4. NANOTECHNOLOGY IN MEDICINE,
WHAT FOR?
 SOLUBILITY ENHANCEMENT (NanoCrystal®
Technology)
 BIOAVAILABILITY ENHANCEMENT
 DIAGNOSIS
 THERAPY
 TARGETING
Doxil®
-Passive targeting(Eg : Doxil®)
-Active targeting(Eg: RONDEL™)

5. SOLUBILITY AND BIOAVAILABILITY
ENHANCEMENT
 Up to 50% of existing drugs
are insoluble
 Thus , bioavailability is
very poor
 Micronization of
insoluble drugs
 Wet-milling process
 Increased solubility
and dissolution rate
 Enhanced Bioavailability

6. DIAGNOSIS
Imaging
technologies
• MRI scanning
• CT
• PET scanning
LAB-ON-CHIP(LOC)

7. Magnetic resonance imaging (MRI)
 Uses a combination of a
large magnet , radio
frequencies and image
reconstruction software to
produce detailed images of
organs and structures
- Non-invasive
- High resolution
- No ionizing radiation
 Usually superparamagnetic
particles are used

8. Advantages of NP-based MRI
contrast agents
• Create image contrast enhancement
• Prolonged retention in circulation
• Tumor targeting
• May also carry anti-tumor agent (―Theragnostics‖)
MRI of melanoma tumors before and after administration of
contrast agents

10. Computed tomography (CT)
 Tomography is a ―splicing‖ of
the
body into various sections
and planes
 Mainly used in the diagnosis of
lung diseases(tuberculosis)
 Ionized NPs are instilled
intrabronchially
 Contrast materials- NC70146
(1-ethoxycarbonyl)((3,5-
acetylamino) -2,4,6-
triiodobenzoate))-nanoparticle
stabilized by surfactant
 Iodinized nanoparticles instilled
into the small airways were

11. Positron Emission Tomography
(PET)
 Diagnostic application that involves
the acquisition of physiologic image
based on the detection of radiation
from the positron
 Positron emission tomography
(PET) using 18F fluorodeoxyglucose
(FDG) has been used successfully in
the diagnosis of various cancers
Advantages of NPs on PET
 Using nanoparticles with PET
allows the quantitation of PET and
the multifunctionality of
nanoparticles to be taken advantage
 Deliver large number of imaging
agents to molecular targets to
achieve high sensitivity
 Different types of imaging agent to
produce multimodality

12. Lab on chip (LOC)
 Lab on chip helps in
disease diagnosis

13. Miniature Imaging Devices
 Imaging has developed a pill
containing a miniature video
system.
 When the pill is swallowed, it
moves through the digestive
system and takes pictures
every few seconds.
 The entire digestive system
can be assessed for tumors,
bleeding, and diseases in
areas not accessible with
colonoscopies and endoscopies
 Nanoprobes (miniature
machines) can attach
themselves to particles in the
body (e.g., antibodies) and
emit a magnetic field.

14. Targeting
Passive targeting
Active targeting

15. PASSIVE TARGETING
 Passive targeting involves the
preparation of drug carrier
complex that can avoid elimination
due to body defence mechanisms
 The complex will keep circulating in
the blood stream and allow itself to
be taken to the target receptor by
some body property(pH,
temperature etc)
 Nanoparticle systems exploit
characteristics of tumor growth for
the use of a passive form of
targeting

16. ENHANCED PERMEABILITY AND
RETENTION (EPR ) EFFECT
• Various anatomical and
functional abnormalities
in tumor cells causes
extravasation(“angiogene
sis”), and other factors
including poor lymphatic
clearance cause retention
of macromolecules – the
phenomenon called EPR.
• It is now the “Golden
Mean” in anti-cancer
drugs
• Though of high
significance with high
MW drugs, this is not
applicable to low MW
ones for obvious reasons

17. FACTORS AFFECTING THE EPR EFFECT OF
MACROMOLECULAR DRUGS IN SOLID TUMOR
 Active angiogenesis and high
vascular density
 Extensive production of vascular
mediators that facilitate
extravasation, including
 Bradykinin
 nitric oxide
 VPF/VEGF
 prostaglandins
 collagenase (matrix
metalloproteinase, MMP)
Defective vascular architecture:
 for example, lack of smooth
muscle layer cells, lack of or
reduced receptors for angiotensin
II, large gap in endothelial cell–
cell junctions, anomalous
 conformation (branching or
stretching etc.).
 Impaired lymphatic clearance of
macromolecules and lipids from

18.  Polymer conjugates, in EPR
context, have many upsides
such as higher T1/2, better
solubility, receptor mediated
drug targeting and better
quality of patient life
 While accelerated EPR can
improve drug delivery and
faster treatment, suppression
of EPR is another approach,
causing necrosis of tumor
cells

19. ACTIVE TARGETING
• On the horizon are nanoparticles that
will actively target drugs to cancerous
cells, based on the molecules that they
express on their cell surface
• Active targeting or Ligand based
targeting
• Specific biological processes such as
Ligand-receptor recognition is used to
accumulate the drug in the tumor cell
• Ligands /homing devices – antibodies,
peptides, vitamins and sugars.

20. Two important qualities of an active targeting
system
• Specificity of the
ligands onto the
receptors
• Capacity to
deliver the
required dose of
drug for required
period of time
SEM RESULTS
SHOWING THE
ENDOCYTOSIS OF NP
TARGETED ACTIVELY

21. SUSTAINED DRUG DELIVERY
 Controlled drug delivery is one which
delivers the drug at a predetermined
rate, for locally or systemically, for a
specified period of time.
 Advantages
 Total dose is low.
 Reduced GI side effects.
 Reduced dosing frequency.
 Better patient acceptance and compliance.
 Less fluctuation at plasma drug levels.
 More uniform drug effect
 Improved efficacy/safety ratio

22. Nanorobots
 What are they?
 Nanorobots are
nanodevices
 To repair or detect
damages and infections.
 Exfuse themselves
“Athrough human excretory
microscopic machine roaming
through the bloodstream, injecting
system.
or taking samples for identification
and determining the concentrations
of different compounds"

23. Nanorobots –
Features
 The powering of the
nanorobots.
 Other sources of energy .
 Will be having onboard
computers.
 Size of 0.5-3 micrometers.
 Carbon is the primary
component.
 Self-replication
 They will be able to
distinguish between different
cell types by checking their
surface antigens. Virus detector

24. Nanorobots – functional
requirements
 A navigational network has
to be installed.
 This will enable the physician
to keep track of the various
devices in the body
 Nano-tracking may be able
to detect tumors that are a
few cells in size. (Alivisatos,
2001)
A single inhaled nanorobot reaches, deeply
inspired into the lungs and attaches to the
tissue surface

25. DENTAL ROBOTS
 A mouthwash full of smart
nanomachines could identify
and destroy pathogenic
bacteria while allowing the
harmless flora of the mouth
to flourish in a healthy
ecosystem
Four remote-controlled nanorobots examine
and clean the subocclusal surfaces of a
patient's teeth, near the gumline.

26.  Emergency
Management:
 The clottocyte
concept
 Clot-inducing
medical nanorobots
with fully-deployed CLOT-INDUCING MEDICAL
netting capable of NANOROBOTS ARE SHOWN IN
VARIOUS STAGES OF CLOT-NETTING
embedding growing DEPLOYMENT.
clot with red cells
and fibrin strands

27. CLOT-INDUCING MEDICAL A REAL LIFE PICTURE OF
ERYTHROCYTES TRAPPED
NANOROBOTS WITH FULLY-
IN THE FIBRIN MESHWORK
DEPLOYED NETTING ARE SHOWN OF A CLOT
EMBEDDED IN A PATCHLIKE GROWING
CLOT WITH RED CELLS AND FIBRIN
STRANDS INVOLVED (A CLOSER

28. The blue, octopus-like nanobot is one of billions of brain cell enhancers. The
central sphere houses a computer, with a storehouse of information equal to
many large libraries

29. Surgical Robotics
 Instead of manipulating surgical
instruments, surgeons use their
thumbs and fingers to move joystick
handles on a control console to
maneuver two robot arms containing
miniature instruments that are
inserted into ports in the patient. The
surgeon’s movements transform large
motions on the remote controls into
micro-movements on the robot arms
to greatly improve mechanical
precision and safety
 A third robot arm holds a miniature
camera, which is inserted through a
small opening into the patient. The
camera projects highly magnified 3-D
images on a console to give a broad
view of the interior surgical site.
(The daVinci Surgical Robotics
System)

31. Nanoengineered Vaccines
 Engineer artificial / synthetic NPs
viruses
 Safe
NP
 Less toxic than other adjuvants
 Cost-effective
 Enhance solubility/delivery of Dendritic Cell (APC) IFNg
IgG2a
vaccine components
B cell IgG1, IgM,
 Co-delivery of antigen/adjuvant MHC II Th2
IL-4
IgA, IgE
MHC I
 Improve cell uptake and
IL-4, IL-5
CD4+ IL-6, IL-10
Th1 T cell
CD8+
trafficking T cell IL-2, IL-3,
IFNg, TNFa
 NP surface can be Humoral
Responses
functionalized Cellular
Responses
 Cell-targeting

32. DiOC18 NPs in DC
Uptake of NPs BY DC
Study performed at NIH/NIAID/VRC ENTRY OF HIV INSIDE THE CEL

33. HIV Vaccine Concept
 A DC-targeted nanoparticle
with conserved proteins Tat
(1-72) and Gag p24 to
generate protective Th1, CTL,
and neutralizing antibody
NIH-NIAID R01 AI058842 response s that may be
further enhanced by co-
delivery of Adjuvants (PRLs)
Dendritic Cell
Toll-like Receptor
(TLR-9)
MHC I DC Mannose
Receptor
Tat (1-72)
PEG
Adjuvant
Mannopentaose
(DC targeting) (PRL)
Gag p24
Tat & Gag p24 antigens: conserved; critical; CTLs detected in LTNPs

34. Achievement And Future
prospects for Nanomedicine:
 1st generation product (2000)
a) Dispersed and contact nanostructure
Ex-:colloids
b) Product incorporating nanostructure
Ex-:Polymer,nanostructured metal
 2nd active nanostructure (2000-2005)
a) bio-active, health effect
Ex-:targeted drugs,biodevices
b) Physico chemical active adaptive structure
Ex-:amplifier, actuators
 3rdNanosystem (2005-2010)
a) Guided assembling
Ex-:robotics, evolutionary biosystems
 4th Molecular nanosystems(2010-2020)
a) Ex-: molecular devices ‘by design’

35. CONCLUSION
 The next BIG thing is really “small”
FUTURE NANO
Humanoid shaped
nanorobots
Respirocytes: Artificial RBC