What We should Know About the
Joseph F. Chiang
Department of Chemistry and
Oneonta, NY 13820
Technological developments for the
Last half Century
Outline of developments:
1. In the middle of the 40’s, the most
important invention: Transistors to
Braintain, et.al., at Bell Laboratories).
This led to the later development of
integrated circuit(IC) and PC
2. In the early 60’s, laser(light amplification
by stimulated emission of radiation).
Everyone is benefited by this
development- music, entertainment,
healthcare, communication, etc.
3. In the early 70’s, Integrated circucit(IC)
and Personal computer(PC) were
developed( main frame computers, such
as IBM 360, CDC 6600, UNIVAC 1108;
Minicomputer-DEC, Gray, etc. were built
4. In the early 80’s, superconductors were
revived. Many medical instruments were
built, such as MRI(Magnetic Resonance
Imaging). The term: NMR(Nuclear
Magnetic Resonance) were avoided
since the word: Nuclear.
We all have some background on
semiconductor, laser, superconductor,
5. The most current development:
Numerous applications in
nanotechnology exist, such as in
electronics, physics, chemistry,
engineering, materials sciences.
My talk will concentrate on application in
What is nanotechnology?
To build matter from atoms/molecules, a
All matters were built historically with top-
Chemistry is a nanotechnology- combining
atoms/molecules to build bulk materials.
Example of Bottom-up Approach:
Proteins are synthesized from lower
molecular weight amino acid precursors by
chemically or biologically mediated
Carbon Nanotubes can synthesized from
graphite sheets in an electric arc oven
by metal catalytic method.
All the above-mentioned materials are built
in nanometers. (1 nano meter = 10-9 meter).
Protein MW Size_________
Hemoglobin 68KDa 4.5x7nm
Lipoprotein 130KDa 20 nm
-globulin 90KDa 4.3x26 nm
Fibrinogen 406KDa 4x76 nm
d=size parameter of fundamental,
biological building block:
MW= molecular weight in unit of dalton.
Some representative nanoparticles:
Quantum Wells, Wire and Dots
• Quantum wells: if one dimension is
reduced to nanoscale while the other two
• Quantum wires: if 2 dimensions reduced to
nanoscale while the third one remains
• Quantum dots: if all 3 dimensions reach
The following chart will give our audience
some idea of scales and nanoscales.
One can visualize the scale from tennis
ball, a period(.), and virus.
Medical Applications are shown as follows
Various molecules were developed as
nanodevices for nanotherapeutic
applications as shown below:
The difference between traditional drug
delivery and nanotherapeutic drug delivery:
Drug Delivery System Technologies:
Oral Drug Delivery
Injection Based Drug Delivery
Transdermal Drug Delivery
Bone Marrow Infusion
Organ System Specific Delivery:
a. Pulmonary Drug Delivery
b. Nasal Delivery to Central Nervous
c. Cardiovascular System(CV)
d. Gastro-Intestinal Track(GI)
e. Genito-Urinary Track(GU)
f. Ocular Drug Delivery
Control Release System:
Novel Packaging and Formulations:
a. Fast Dissolving Tablets
b. Chewable Tablets
c. Solubility Enhancement
Targeted Drug Delivery:
a. Polymer and Collagen System
b. Particle-based System:
1.Therapeutic Monoclonal Antibodies,
4.Modified Blood Cells,5.Nanoparticles,
6.Viral Assisted Intracellular Gene
Delivery, 7.Non-viral Intracellular Gene
Goals of Nano-therapeutics
1. Ways to treat Disease
Requirements of Nano therapeutic
• Devices should be non-invasive
• Devices target therapeutics payloads to
site of disease.
• Devices should maximize therapeutic
benefit and minimize undesired side
To deliver drug directly to cells.
(The effective drug treatment is getting the
medication to exactly the right spot)
Research report in “Science”:
Methods to develop tiny containers of
nanocomposites to distribute drugs to
specific spot within individual cells.
Development of two types of polymers- Micelle:
hydrophobic end facing inward, and hydrophilic
end facing outward ( Radoslav Aavic, McGill)
Dimension: 20-45 nm.
Using fluorescent light to track the micelle’s
journey and to discover the whereabouts of the
tiny container which passes through the wall of a
rat cell, but did not enter the cell’s nucleus. It
also did not penetrate other part of the cell, as
Nanoceramic drug delivery
1. Reducing toxicity to non-diseased cells,
2. Increasing drug efficiency,
3. Being able to target and to control
drug release with high precision.
(Several anti-cancer drugs fail in their
desired clinical activity due to lack of
specific target delivery.)
Glass microsphere of 17Y2O3-19Al2O3-
64SiO2(mol %) composition, 20-30 m
diameter-effective for targeted radiotherapy
of liver cancer( 89Y is non-radioactive, can
be activated by neutron bombardment to
90Y, a -emitter(t =64.1 h).
One of the great promises of
nanotechnology- to increase control of
Understanding of disease-open the door to
therapy for treating disease.
Nanotherapeutic is one of the
nanotechnology applications in treating
• Nanotherapeutic devices are created to
find the target and to correct it.
• Immunotoxins-one component binds to
target cells, the other component is the
poison that kills the cell.
• Liposomes-artificial membranes, under
specific conditions forming small, closed
vesicles composed of a lipid bilayer that
encloses a small droplet of water.
Liposome size-20 nm-10m to deliver
• Gene Therapy- with understanding of
human genome, one can understand
and correct genetic defect.
• Therapy is to correct a missing or defect
Injection of the spheres into a diseased liver
through the hepatic artery where they are
entrapped in small blood vessels to block
blood supply to cancer cells and
irradiating β ray to cancerous cells.
The development of Targeted Nano
( by Triton BioSystem with Army Research
The TNT system attacks cancer in 3 steps.
1. The patient receives a simple infusion
containing trillions of bioprobes, each of
which is a nanoscale magnetic sphere
bound to an antibody,
2. The bioprobes will seek and attach to
cancer cells in the bloodstream.
3. Physicians will switch on the magnetic
field in the region of the cancer. This will
cause the bioprobes to heat up to kill the
cancer cells within minutes.
A tumor or cancerous cell can be destroyed at
43oC. Normal cells can be kept alive at ~49 oC.
When ferri- or ferro-magnetite materials are
implanted, heating at alternating magnetic field
can kill the cancerous cells. If the pore of the
magnetic materials is decreased to nanoscale,
cancer cells can be destroyed.
Use of ferromagnetic glass ceramic
containing 36 wt% of magentite(Fe3O4),
200nm diameter in CaO-SiO2 matrix.
The cancerous cells in the canal of rabbit
tibia were destroyed when the device is
inserted into tibia and placed under an
alternating magnetic field of 300 Oe at
100 KHz.(Kokubo, et al.)
Existing therapies-surgical, resection,
radiotherapy, and chemotherapy-
Nanotherapeutic devices can be specifically
delivered to tumor by virtue of the size,
Therapeutic devices with cytoxins can not
leave the normal cells, but can leak to
2. Cardiovascular Application of
Current tissue engineering approaches
involve synthesis of 3-D, porous scaffolds
that allow, adhesion, growth, and
proliferation of seeded cells to generate
MEMS technology and nanoscale control
of molecular events &interaction has been
applied to the development of
3. Nanotherapeutics & Specific Host
4. Nanotherapeutic Vaccines
5. Antibody Response to
6. Special Device Applications:
a. Biosensors detect glucose level for
management of diabetes:
Implanted sensors and non-invasive
sensors are underdevelopment to monitor
glucose level with glucose oxidase which
combine glucose and O2 to form gluconic
acid and H2O2. Pt electrode is used to
measure H2O2 level.
b. A biosensor using hemolysin to
detect short strand of DNA. Hemolysin
is embedded in a membrane separating
2 chambers which draws ions from one
to another. When nanopores are
blocked, an abrupt change in current is
detected(Chamber dimensions: one
with 3-4 nm in diameter and the other
with 1.4 nm in diameter).
c. Antibodies used as a biosensor for
blood type tester-composed of a
collection of antibodies that recognize
specific sugars on the surface of red
blood cells. The antibody is added to
the blood, and if the particular blood
type is present in the cells, the antibody
is bind to the surface, sticky cells
together. The result is that a clumping of
cells can be detected by human eye.
Micro and Nanotechnology in Drug Delivery
• Synthesis and Preparations of
nanoporous inorganic & organic
• Use of biomolecules for targeting,
adhesion, and biointerfacing
• Nanofabricated & micro patterned drug
• Formation & fabrication of
nanoparticulate system modified with
natural biological ligands.
Present Focuses of Therapeutic
Patients & Physicians
• Improve drug delivery and
• Enhance drug stability
• Increase compliance
• Potential for local delivery-
How Can Micro and
Micro and nanofabrication allow for:
Control for shape
Control for size
Asymmetrical 3D design
Requirements for Development
of new Biomaterials for Medical
Understanding of cell and biology,
tissue engineering, drug delivery and
other medical processes are required
for development in microscale,
nanoscale and biomimetics(bio-
inorganic chemistry, a bio-inspired
Nanoceramics development leads to
1. Production of new implantable surface
modified- medical devices,
2. Increase bioactivity, tissue
regeneration and engineering,
3. Help cancer treatment, drug and gene
4. Deliver oxygen to damaged tissues,
5. Imaging for minimal invasive surgery,
6. Treat bacterial and viral infections.
Definition of Biomaterials
Biomaterials are a non-drug substance
suitable for inclusion in systems of
bodily tissue or organs. These materials
are capable of being in direct contact
with body fluid and tissues for prolonged
period without side effect.(50% of
biomaterials are used in orthopedic and
Biomaterials and Bioceramics
Foreign materials such as biomaterials in
contact with a living body can not be 100%
compatible. But materials at nanoscale
react in many ways: bioinert, bioresorbale,
They can be accepted by body, but do not
interact or react with the physiological
environment, such as alumnia.
They are surface-reactive and dissolve in
physiological environment to be replaced
by soft/hard tissue.
Reacting with tissue and forming
chemical bonding. Hyroxyapatite is an
(See reference: Hench, et al., Ann. NY
Academy of Science, 523, 54, 1988.)
The Advantage of Improving
bioceramics in nanoscale:
• Maintaining the physical functions
• Providing more interactions with the host.
Types of Applications
1. Bone Replacement:
Nanotechnology can be applied to the
production of bonelike synthetic
nanopowder and coatings of
HAp has been used for orthopedic and
dental nanocomposites. (Particle size:
15-20 nm diameter by 40 nm thickness)
HAp- a bioactive nanocrystallline
(Ca, Mg, Na)10(PO4, CO3)6(OH)2
2. Calcium Phosphate Coatings
Co-Cr and titanium-based alloys are used
for thin film HAp coatings by thermal spray,
pulsed laser deposition, sputtering,
electro-deposition, or sole get technique.
3. Simulated Body Fluid
Nanoscale coatings and surface-
modification techniques can be applied to
body-interactive materials- nanoceramics:
Promoting regeneration of tissue
Restoring physiological function.
4. Nano- and Macro ceramics for
• Purpose of drug delivery.
• Having drug at specific site.
• Reducing toxicity to non-diseased cell.
• Nanoceramic systems can increase drug
• It also can target and control drug release.
• Glass microsphere of 17Y2O3-19Y2O3-
4Al2O3-64SiO2(mole %) has shown to
be effective for radiotherapy of liver
• The non-radioactive 89Y can be
activated by 90Y with half-life of 64.1
hour (90Y is a -emitter isotope)
5. Bioengineering Applications
Microtechnology and nanotechnology can
be used for fabrication of biodevices:
a. planar devices(biosensor, arrays, DNA
b. micro/nano biodevices(nanoscale,
biosensor, large-scale, integrated
c. artificial organs or tissues
d. microfluidic devices and biochips
(lab on a chip).
e. Biomimetics engineering
f. guided drug delivery to bio-MEMS
6. Tissue Engineering
• Use of stem cells( type of cell having
ability to reproduce for a long period)
incorporated into bioceramics to give rise
cells that can make up tissues and organs
• The nanoscale cultured cell/bioceramic
composites can be used to fill gap in bone
Nanoceramics for Gene & Drug
Layered double hydroxides(LDHs)-
Gene or drug delivery into biological
cells-a gene or drug delivery carrier
Composition of LDHs:
Where M(II)-divalent cation
A =interlayer anion,
n- =charge on the interlayer ion.
(Inorganic or organic anions can be
introduced between hydroxide layer by ion
exchange or precipitation.)
Biofunctional molecules- nucleoside
monophosphates, ATP, DNA,
flourescein-5-isothiocyanate, etc can
be intercalated into hydroxide layer
to form bio-LDH nanohybrids
Controlled Release of Interlayer
The biomolecules stored in LDH’s can
be released under acidic condition.
Preparation of Nanoparticles of LDHs
• The bottom-up approach can make
materials from atomic to mesoscopic
and macroscopic scales.
• Nanotechnology can have impact on
nanophotonics, separation techniques,
catalysis, thermal coatings, sensor,
cosmetics,nanomedicine, ceramics, and
polymer composite applications.