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NANOBIOMEDICI
NE
SUBMITTED BY
SHAMJA R
II MSC BIOTECHNOLOGY
SNGC
CONTENTS
INTRODUCTION
NANOTECHNOLOGY
DRUG DELIVERY SYSTEM
EXPERIMENTAL PREPARATION OF GOLD NANOPARTICLE
MEDICAL DIAGNOSTICS
BIOMEDICAL APPLICATIONS
CONCLUSION
INTRODUCTION
• There is no nanomedicine, there is nanotechnology in medicine. Even if the
expression “nanomedicine” has been widely used for a couple of years, it is
more proper to refer to “nanotechnology enabled medicine” in different sub-
areas of medicine such as diagnostics, therapy or monitoring.
• Nanomedicine is a relatively new field of science and technology. The
investigated diagnostic applications can be considered for in vitro as well as for
in vivo diagnosis. In vitro, the synthesised particles and manipulation or
detection devices allow for the recognition, capture, and concentration of
biomolecules. In vivo, the synthetic molecular assemblies are mainly designed
as a contrast agent for imaging.
• A second area exhibiting a strong development is “nanodrugs” where
nanoparticles are designed for targeted drug delivery. The use of such carriers
improves the drug biodistribution, targeting active molecules to diseased
tissues while protecting healthy tissue.
• A third area of application is regenerative medicine where nanotechnology
allows developing biocompatible materials which support growth of cells used
in cell therapy.
NANOTECHNOLOGY
 Nanotechnology is the term given to those areas of science and engineering where phenomena that take
place at dimensions in the nanometre scale are utilized in the design, characterization, production, and
application of materials, structures, devices, and systems.
 "nano" means one-billionth, or 10-9; therefore, one nanometre is one-billionth of a meter.
 Areas of Nanotechnology
METHODS OF NANOPARTICLE SYNTHESIS
1. Top-Down Approach
2. Bottom-Up Approach
DRUG DELIVERY SYSTEM
• The untargeted drug delivery is less sophisticated. The drug that enters the body affects
both the infected cells as well as the normal cells. Therefore, it creates lot of side effects
and may kill the normal cells.
• The targeted drug delivery is done with the help of the nanotube. The drugs are attached
to the nanotube. The nanotube has a Guider that helps to identify and differentiate
normal cells and infected cells. The Guider act as an organic GPS.
• This is a targeted Nanomedicine delivery method where the drug enters only the infected
cells. It will not enter the normal cells and therefore the side effects will be minimum.
EXPERIMENTAL PREPARATION OF GOLD
NANOPARTICLE
• The reason why Gold Nanoparticles are used is because it is easy to graft organic molecules on the gold surface.
• There are 3 phases for the preparation of Gold Nanoparticle:
1.Nucleation
2.Growth phase
3.Termination phase
AIM:
 Preparation of Gold Nanoparticle in solution
 Demonstrate how a laser beam is used to test for their presence
 Demonstrate how increasing the size of the nanoparticle changes the colour of Gold
REAGENTS AND MATERIALS REQUIRED:
 20mL of gold hydrogen tetrachloride solution
 2mL of Sodium citrate solution
 1mL of Sodium chloride solution
 Distilled water
 Magnetic stirrer and hot plate combination
•
PROCEDURE
PART 1: Making Gold nanoparticles by mixing gold chloride and Sodium citrate solution
A nanoparticle has a diameter of 10 to 100 nm and is made up of a cluster of atoms.
• Add 20mL of gold solution into the conical flask and heat the solution for 5 minutes until
it gets boiled and stir it well in a magnetic stirrer to heat up evenly.
• Keep a watch glass on the top of the conical flask to stop the solution evaporating as it
heats. After 5 minutes of boiling, remove the watch glass and add the 2mL citrate
solution which facilitates a chemical reaction and produces uniformly sized particles.
• The colour gradually changes from a light gold to blue colour phase. As we continue
stirring the colour again changes to bright red. The red colour indicates that we have
produced nano-sized gold particles of around 10 to 20 nm in diameter.
• The gold ions react with citrate ions to form gold atom.
• As well as acting as acting as a reducing agent in producing the gold atoms citrate ions
act as a shielding agent wrapping around the cluster of atoms which constitute the
nanoparticles.
• This creates an electrostatic sheath around each nanoparticle, which prevents
agglomeration and stabilizes the particles in solution.
PART 2: Confirming we have produced gold nanoparticles
• Firstly, remove the red solution from the stirrer and allow it to cool.
• Then transfer some of the solution into a test tube. Pour distilled water and gold chloride solution into two other test tubes. Now we
have 3 different solutions in 3 test tubes.
• Now shine the red laser beam through each of the test tubes to find out which, if any, contains gold nanoparticles.
• As the gold nanoparticle is a colloid we can’t see them, but we can usually detect them by the way they react to the light.
• When the laser beam is made to shine on test tubes of both the distilled water and gold chloride solution, we could see that
there is no visible passage of light and is just a bright spot on either side.
• Now shine the red laser through the test tube that we hope has the gold nanoparticles.
• we can observe the passage of light as a red beam from one side of the test tube to the other. The suspended nanoparticles
are reflecting and scattering the light as it passes through the solution. A response known as the “Tyndall effect”.
• Thus, we can confirm the presence of gold nanoparticles
. PART 3: Changing the size changes the colour
• Take the Gold nanoparticle solution in two test tubes.
• To one of the test tubes add a few drops of sodium chloride solution.
• Shake it and observe the results. We will get a darker solution.
• By adding sodium chloride to the original gold nanoparticles, we have caused the particles to increase in size which affects the
way they reflect light and therefore changes their observed colour.
• Adding sodium chloride disturbs the electrostatic sheath around each nanoparticle resulting in positive attraction between
nanoparticles agglomeration and therefore particles larger than 20 nm.
Thus, we have created nanoparticles of different sizes and observed how their size determines their colour.
 Steps for making Au nanocrystals:
H2AuCl4 +3e- =Au
When the gold hydrogen tetrachloride dissolves in water it exists in ionic form. Then when we drop the sodium citrate into this
the gold is reduced.
Au3+_______ Au
The Citrate ions act as the stabilizing agent. Therefore, the Au combines with another Au in the solution and become a bulk
material.
The dots represented in the image are the ions (single and independent)
MEDICAL DIAGNOSTICS
• Nanotechnology enables further refinement of diagnostic techniques, leading to high throughput screening (to test
one sample for numerous diseases, or screen large numbers of samples for one disease) and ultimately point-of-
care (POC) diagnostics.
• An in vitro diagnostic tool can be a single biosensor, or an integrated device containing many biosensors. A biosensor is a sensor
that contains a biological element, such as an enzyme, capable of recognising and ‘signalling’ (through some biochemical change)
the presence, activity or concentration of a specific biological molecule in solution.
• In vivo diagnostics In vivo diagnostics refer in general to imaging techniques, but also covers implantable
devices. Nanoimaging includes several approaches using techniques for the study of in vivo molecular events
and molecules manipulation. Imaging techniques cover advanced optical imaging and spectroscopy, nuclear
imaging with radioactive tracers, magnetic resonance imaging, ultrasound, optical and X-ray imaging, all of
which depend on identifying tracers or contrast agents that have been introduced into the body to mark the
disease site
• Medical imaging has advanced from a marginal role in healthcare to become an essential diagnostic tool over
the last 25 years. Molecular imaging and image guided therapy is now a basic tool for monitoring disease and
in developing almost all the applications of in vivo nanomedicine.
• Targeted molecular imaging is important for a wide range of diagnostic purposes, such as the identification
of the locus of inflammation, the localisation and staging of tumors, the visualisation of vascular structures
or specific disease states and the examination of anatomy. It is also important for research on controlled
drug release, in assessing drug distributions, and for the early detection of unexpected and potentially
dangerous drug accumulations.
 The convergence of nanotechnology and medical imaging opens the doors to a revolution in
molecular imaging (also called nano-imaging) in the foreseeable future, leading to the
detection of a single molecule or a single cell in a complex biological environment.
 Current imaging methods can only readily detect cancers once they have caused a visible
change to a tissue, by which time thousands of cells will have proliferated and perhaps
metastasised. And even when visible, the tumor nature – malignant or benign – and the
characteristics that might make it responsive to a particular treatment must be assessed
through biopsies. Imagine instead if cancerous or even pre-cancerous cells could somehow
be tagged for detection by conventional scanning devices.
 Two things would be necessary – first something that specifically identifies a cancerous cell
and second something that enables it to be seen – and both can be achieved through
nanotechnology.
 For example, antibodies that identify specific receptors found to be over-expressed in
cancerous cells can be coated onto nanoparticles such as metal oxides which produce a high
contrast signal on Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans .
 Once inside the body, the antibodies on these nanoparticles will bind selectively to cancerous
cells, effectively lighting them up for the scanner. Similarly, gold particles could be used to
enhance light scattering for endoscopy techniques like colonoscopies.
 Nanotechnology will enable the visualisation of molecular markers that identify specific
stages and types of cancers, allowing physicians to see cells and molecules undetectable
through conventional imaging.
o . Implants, sensors Implantable devices for in vivo diagnostics.
o Nanotechnology also has many implications for in vivo diagnostic devices such as
the swallowable imaging ‘pill’ and new endoscopic instruments. Monitoring of
circulating molecules is of great interest for some chronic diseases such as diabetes
or AIDS.
o Continuous, smart measurement of glucose or blood markers of infection
constitutes a real market for implantable devices.
o Miniaturisation for lower invasiveness, combined with surface functionalisation and
the ‘biologicalisation’ of instruments will help increase their acceptance in the body.
Autonomous power, self-diagnosis, remote control and external transmission of
data are other considerations in the development of these devices.
o Nanosensors, for example used in catheters, will also provide data to surgeons.
o Nanoscale entities could identify pathology/defects; and the subsequent removal or
correction of lesions by nano-manipulation could also set a future vision.
o Nano-harvesting of biomarkers. Researchers attempting to identify disease-related
biomarkers in blood face two major problems, each of which the new polymer-
based nanoparticles appear to overcome.
o One issue is that two proteins – albumin and immunoglobulin – account for 90
percent of the molecules in blood, whereas any potential biomarkers are likely to be
present at only trace levels.
o Nano-biopsy. Brain tumours are often the hardest cancers to diagnose in the human
body. For diagnosis in other tissues, biopsies allow to determine whether a tumour
is benign or malignant. But removing brain tissue should be avoided due to the
specificity of this organ
BIOMEDICAL APPLICATIONS
Biomedical applications of smart materials can be divided into three categories:
(1) implants and stents, such as bone plates and marrow needles
(2) surgical and dental instruments, devices, and fixtures, such as orthodontic fixtures and biopsy
forceps
(3) devices and instruments for medical checkups, such as ultrasonic devices.
ADVANTAGES OF NANOBIOMEDICINE
o Drug delivery to the exact location
o Lower side effects
o Molecular targeting by nanoengineered devices
o Detection is relatively easy
o No surgery required
o Diseases can be easily cured
DISADVANTAGES OF NANOBIOMEDICINE
 Not fully practical yet
 High cost
 If nanoparticles have poor solubility they can cause cancer.
This is because the nanoparticles have a greater surface
area to volume ratio which increases the chemical and
biological reactivity.
 The ethical issues concerned with nanobiotechnologies are
related to Health, Safety, Medical, Legal, Social and
Environmental issues. Other ethical issues include
Governance of Research, Economic Displacements,
Anthropological Aspects and Transhumanists.
CONCLUSION
• Like most high technologies and taking into account the high regulation of medical sector, it
takes 10–15 years to any advanced medical technology before reaching the market.
Considering significant efforts put in nanomedicine related basic research in the early 2000’s,
it is expected that a significant number of approved nanodrugs or nanodevices will be
approved in the early 2010’s. So far 22 nanodrugs are approved by FDA, and many more are
under clinical trials phase II or even III. The same situation occurs in Europe with
approximately 25 on going clinical trials in 2010.
• In the same time, more SMEs and spin-off companies target medical applications using
nanotechnologies, sometimes niche markets, contributing to the validation of innovative
concepts. It is easy forecasting that large companies, like pharma, imaging or diagnostics
companies will help some of the most promising companies to reach the market.
• Then we will see what the real medical applications are for which nanotechnology brings a real
added value in a cost effective manner. Nanomedicine is one of the most rapidly growing fields of
translational medicine and has made marked impacts in terms of alleviation of toxicity and enhancement of
efficacy for therapies.
• The convergence of chemistry and nanomedicine may allow the development of patient-individualized
treatments (e.g., on-demand drug delivery and self-regulated drug delivery) and provide new therapeutic
modalities (e.g., new therapeutic formulations and imaging modalities). Progress in this field will depend on the
fundamental understanding of organic and polymer chemistry, materials engineering, biology, and clinical

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NANOMEDICINE PPT.pptx

  • 2. CONTENTS INTRODUCTION NANOTECHNOLOGY DRUG DELIVERY SYSTEM EXPERIMENTAL PREPARATION OF GOLD NANOPARTICLE MEDICAL DIAGNOSTICS BIOMEDICAL APPLICATIONS CONCLUSION
  • 3. INTRODUCTION • There is no nanomedicine, there is nanotechnology in medicine. Even if the expression “nanomedicine” has been widely used for a couple of years, it is more proper to refer to “nanotechnology enabled medicine” in different sub- areas of medicine such as diagnostics, therapy or monitoring. • Nanomedicine is a relatively new field of science and technology. The investigated diagnostic applications can be considered for in vitro as well as for in vivo diagnosis. In vitro, the synthesised particles and manipulation or detection devices allow for the recognition, capture, and concentration of biomolecules. In vivo, the synthetic molecular assemblies are mainly designed as a contrast agent for imaging. • A second area exhibiting a strong development is “nanodrugs” where nanoparticles are designed for targeted drug delivery. The use of such carriers improves the drug biodistribution, targeting active molecules to diseased tissues while protecting healthy tissue. • A third area of application is regenerative medicine where nanotechnology allows developing biocompatible materials which support growth of cells used in cell therapy.
  • 4. NANOTECHNOLOGY  Nanotechnology is the term given to those areas of science and engineering where phenomena that take place at dimensions in the nanometre scale are utilized in the design, characterization, production, and application of materials, structures, devices, and systems.  "nano" means one-billionth, or 10-9; therefore, one nanometre is one-billionth of a meter.  Areas of Nanotechnology
  • 5. METHODS OF NANOPARTICLE SYNTHESIS 1. Top-Down Approach 2. Bottom-Up Approach
  • 6. DRUG DELIVERY SYSTEM • The untargeted drug delivery is less sophisticated. The drug that enters the body affects both the infected cells as well as the normal cells. Therefore, it creates lot of side effects and may kill the normal cells. • The targeted drug delivery is done with the help of the nanotube. The drugs are attached to the nanotube. The nanotube has a Guider that helps to identify and differentiate normal cells and infected cells. The Guider act as an organic GPS. • This is a targeted Nanomedicine delivery method where the drug enters only the infected cells. It will not enter the normal cells and therefore the side effects will be minimum.
  • 7. EXPERIMENTAL PREPARATION OF GOLD NANOPARTICLE • The reason why Gold Nanoparticles are used is because it is easy to graft organic molecules on the gold surface. • There are 3 phases for the preparation of Gold Nanoparticle: 1.Nucleation 2.Growth phase 3.Termination phase AIM:  Preparation of Gold Nanoparticle in solution  Demonstrate how a laser beam is used to test for their presence  Demonstrate how increasing the size of the nanoparticle changes the colour of Gold REAGENTS AND MATERIALS REQUIRED:  20mL of gold hydrogen tetrachloride solution  2mL of Sodium citrate solution  1mL of Sodium chloride solution  Distilled water  Magnetic stirrer and hot plate combination •
  • 8. PROCEDURE PART 1: Making Gold nanoparticles by mixing gold chloride and Sodium citrate solution A nanoparticle has a diameter of 10 to 100 nm and is made up of a cluster of atoms. • Add 20mL of gold solution into the conical flask and heat the solution for 5 minutes until it gets boiled and stir it well in a magnetic stirrer to heat up evenly. • Keep a watch glass on the top of the conical flask to stop the solution evaporating as it heats. After 5 minutes of boiling, remove the watch glass and add the 2mL citrate solution which facilitates a chemical reaction and produces uniformly sized particles. • The colour gradually changes from a light gold to blue colour phase. As we continue stirring the colour again changes to bright red. The red colour indicates that we have produced nano-sized gold particles of around 10 to 20 nm in diameter. • The gold ions react with citrate ions to form gold atom. • As well as acting as acting as a reducing agent in producing the gold atoms citrate ions act as a shielding agent wrapping around the cluster of atoms which constitute the nanoparticles. • This creates an electrostatic sheath around each nanoparticle, which prevents agglomeration and stabilizes the particles in solution.
  • 9. PART 2: Confirming we have produced gold nanoparticles • Firstly, remove the red solution from the stirrer and allow it to cool. • Then transfer some of the solution into a test tube. Pour distilled water and gold chloride solution into two other test tubes. Now we have 3 different solutions in 3 test tubes. • Now shine the red laser beam through each of the test tubes to find out which, if any, contains gold nanoparticles. • As the gold nanoparticle is a colloid we can’t see them, but we can usually detect them by the way they react to the light. • When the laser beam is made to shine on test tubes of both the distilled water and gold chloride solution, we could see that there is no visible passage of light and is just a bright spot on either side. • Now shine the red laser through the test tube that we hope has the gold nanoparticles. • we can observe the passage of light as a red beam from one side of the test tube to the other. The suspended nanoparticles are reflecting and scattering the light as it passes through the solution. A response known as the “Tyndall effect”. • Thus, we can confirm the presence of gold nanoparticles
  • 10. . PART 3: Changing the size changes the colour • Take the Gold nanoparticle solution in two test tubes. • To one of the test tubes add a few drops of sodium chloride solution. • Shake it and observe the results. We will get a darker solution. • By adding sodium chloride to the original gold nanoparticles, we have caused the particles to increase in size which affects the way they reflect light and therefore changes their observed colour. • Adding sodium chloride disturbs the electrostatic sheath around each nanoparticle resulting in positive attraction between nanoparticles agglomeration and therefore particles larger than 20 nm. Thus, we have created nanoparticles of different sizes and observed how their size determines their colour.  Steps for making Au nanocrystals: H2AuCl4 +3e- =Au When the gold hydrogen tetrachloride dissolves in water it exists in ionic form. Then when we drop the sodium citrate into this the gold is reduced. Au3+_______ Au The Citrate ions act as the stabilizing agent. Therefore, the Au combines with another Au in the solution and become a bulk material. The dots represented in the image are the ions (single and independent)
  • 11. MEDICAL DIAGNOSTICS • Nanotechnology enables further refinement of diagnostic techniques, leading to high throughput screening (to test one sample for numerous diseases, or screen large numbers of samples for one disease) and ultimately point-of- care (POC) diagnostics. • An in vitro diagnostic tool can be a single biosensor, or an integrated device containing many biosensors. A biosensor is a sensor that contains a biological element, such as an enzyme, capable of recognising and ‘signalling’ (through some biochemical change) the presence, activity or concentration of a specific biological molecule in solution. • In vivo diagnostics In vivo diagnostics refer in general to imaging techniques, but also covers implantable devices. Nanoimaging includes several approaches using techniques for the study of in vivo molecular events and molecules manipulation. Imaging techniques cover advanced optical imaging and spectroscopy, nuclear imaging with radioactive tracers, magnetic resonance imaging, ultrasound, optical and X-ray imaging, all of which depend on identifying tracers or contrast agents that have been introduced into the body to mark the disease site • Medical imaging has advanced from a marginal role in healthcare to become an essential diagnostic tool over the last 25 years. Molecular imaging and image guided therapy is now a basic tool for monitoring disease and in developing almost all the applications of in vivo nanomedicine. • Targeted molecular imaging is important for a wide range of diagnostic purposes, such as the identification of the locus of inflammation, the localisation and staging of tumors, the visualisation of vascular structures or specific disease states and the examination of anatomy. It is also important for research on controlled drug release, in assessing drug distributions, and for the early detection of unexpected and potentially dangerous drug accumulations.
  • 12.  The convergence of nanotechnology and medical imaging opens the doors to a revolution in molecular imaging (also called nano-imaging) in the foreseeable future, leading to the detection of a single molecule or a single cell in a complex biological environment.  Current imaging methods can only readily detect cancers once they have caused a visible change to a tissue, by which time thousands of cells will have proliferated and perhaps metastasised. And even when visible, the tumor nature – malignant or benign – and the characteristics that might make it responsive to a particular treatment must be assessed through biopsies. Imagine instead if cancerous or even pre-cancerous cells could somehow be tagged for detection by conventional scanning devices.  Two things would be necessary – first something that specifically identifies a cancerous cell and second something that enables it to be seen – and both can be achieved through nanotechnology.  For example, antibodies that identify specific receptors found to be over-expressed in cancerous cells can be coated onto nanoparticles such as metal oxides which produce a high contrast signal on Magnetic Resonance Images (MRI) or Computed Tomography (CT) scans .  Once inside the body, the antibodies on these nanoparticles will bind selectively to cancerous cells, effectively lighting them up for the scanner. Similarly, gold particles could be used to enhance light scattering for endoscopy techniques like colonoscopies.  Nanotechnology will enable the visualisation of molecular markers that identify specific stages and types of cancers, allowing physicians to see cells and molecules undetectable through conventional imaging.
  • 13. o . Implants, sensors Implantable devices for in vivo diagnostics. o Nanotechnology also has many implications for in vivo diagnostic devices such as the swallowable imaging ‘pill’ and new endoscopic instruments. Monitoring of circulating molecules is of great interest for some chronic diseases such as diabetes or AIDS. o Continuous, smart measurement of glucose or blood markers of infection constitutes a real market for implantable devices. o Miniaturisation for lower invasiveness, combined with surface functionalisation and the ‘biologicalisation’ of instruments will help increase their acceptance in the body. Autonomous power, self-diagnosis, remote control and external transmission of data are other considerations in the development of these devices. o Nanosensors, for example used in catheters, will also provide data to surgeons. o Nanoscale entities could identify pathology/defects; and the subsequent removal or correction of lesions by nano-manipulation could also set a future vision. o Nano-harvesting of biomarkers. Researchers attempting to identify disease-related biomarkers in blood face two major problems, each of which the new polymer- based nanoparticles appear to overcome. o One issue is that two proteins – albumin and immunoglobulin – account for 90 percent of the molecules in blood, whereas any potential biomarkers are likely to be present at only trace levels. o Nano-biopsy. Brain tumours are often the hardest cancers to diagnose in the human body. For diagnosis in other tissues, biopsies allow to determine whether a tumour is benign or malignant. But removing brain tissue should be avoided due to the specificity of this organ
  • 14. BIOMEDICAL APPLICATIONS Biomedical applications of smart materials can be divided into three categories: (1) implants and stents, such as bone plates and marrow needles (2) surgical and dental instruments, devices, and fixtures, such as orthodontic fixtures and biopsy forceps (3) devices and instruments for medical checkups, such as ultrasonic devices. ADVANTAGES OF NANOBIOMEDICINE o Drug delivery to the exact location o Lower side effects o Molecular targeting by nanoengineered devices o Detection is relatively easy o No surgery required o Diseases can be easily cured DISADVANTAGES OF NANOBIOMEDICINE  Not fully practical yet  High cost  If nanoparticles have poor solubility they can cause cancer. This is because the nanoparticles have a greater surface area to volume ratio which increases the chemical and biological reactivity.  The ethical issues concerned with nanobiotechnologies are related to Health, Safety, Medical, Legal, Social and Environmental issues. Other ethical issues include Governance of Research, Economic Displacements, Anthropological Aspects and Transhumanists.
  • 15. CONCLUSION • Like most high technologies and taking into account the high regulation of medical sector, it takes 10–15 years to any advanced medical technology before reaching the market. Considering significant efforts put in nanomedicine related basic research in the early 2000’s, it is expected that a significant number of approved nanodrugs or nanodevices will be approved in the early 2010’s. So far 22 nanodrugs are approved by FDA, and many more are under clinical trials phase II or even III. The same situation occurs in Europe with approximately 25 on going clinical trials in 2010. • In the same time, more SMEs and spin-off companies target medical applications using nanotechnologies, sometimes niche markets, contributing to the validation of innovative concepts. It is easy forecasting that large companies, like pharma, imaging or diagnostics companies will help some of the most promising companies to reach the market. • Then we will see what the real medical applications are for which nanotechnology brings a real added value in a cost effective manner. Nanomedicine is one of the most rapidly growing fields of translational medicine and has made marked impacts in terms of alleviation of toxicity and enhancement of efficacy for therapies. • The convergence of chemistry and nanomedicine may allow the development of patient-individualized treatments (e.g., on-demand drug delivery and self-regulated drug delivery) and provide new therapeutic modalities (e.g., new therapeutic formulations and imaging modalities). Progress in this field will depend on the fundamental understanding of organic and polymer chemistry, materials engineering, biology, and clinical