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CY-241 Nanotechnology

NanoMedicine
Ashish singh

B10007

Ashwini kumar B10008
Abstract |Nanotechnology is an emerging scientific field creating materials, devices and
systems at the molecular level. By being able to work at the ultra-small scale( billionth of a
metre), nanotechnology is being used to deliver innovations in sectors including
health.Nanomedicine is the medical application of Nanoscience which ranges application of
Nanomaterials to Nanoelectronic biosensors and even future applications of molecular
technology. Around 130 nano-tech based drugs and delivery systems are been developed
worldwide (Nature materials, April 2006) .
Nanomedicine exploits the improved physical, chemical and biological properties of materials at
the nanoscale, and offers the potential to enable early detection, prevention, improved diagnosis
and imaging, treatment of diseases. Nanomedicine includes targeted delivery and regenerative
medicine; it interfaces nanomaterials (surfaces, particles, etc) or analytical instruments with
"living" human material (cells, tissue, body fluids).Nanomedicines are solution to some disease
like Cancer, diabetics, cardiovascular diseases, multiple sclerosis, Alzheimer's and Parkinson's
disease.
Uses of NanoMedicine :


Targeted drug delivery



Diagnosis and Imaging



Regenerative medicines

Targeted drug delivery
Target drug delivery seeks to concentrate medicine to diseased cells/tissues and organs. This is in
contrast to current drug delivery trends were a medication is generally administered through the
blood supply resulting in only a small amount of the drug reaching the affected area.
Another good example is Cancer treatment through chemotherapy, in which cancer effected cell
are radiated ,but this cause severe damage to unaffected cells to reduce damaging of unaffected
cells we directly target to the diseased cells by Nanomedicines.
Diagnosis and Imaging (Muldoon, et al., 2005)
NanoMedicine researchers seek to identify and cure life-threatening diseases at the earliest stage.
Researchers are exploring ways for nanotechnology and imaging instruments to better analysis
disease, while offering less painful and evasive methods to patients. Imaging is the strategies to
identify the cancer type of diseases. The effected cell or part of the body show different color or
different property than normal cells we can identify difference in diagnosis and imaging. It show
dark spot. Quantum dot technique used to imaging the effected cells.
The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant
brain tumors and other central nervous system (CNS) diseases.
Various imaging techniques:
1. PET Imaging of Gliomas:PET imaging can be helpful in differentiating low-grade
gliomas,high-grade tumors, and radiation necrosis and allowsdetermination of important
clinical parameters such as metabolism.
2. Tracking Magnetically Labeled Stem Cells:Various approaches have been developed
using coated SPIO nanoparticles to magnetically label stem cells and other
mammaliancells for cellular MR imaging.14 Ferumoxides, a SPIOapproved by the
United States Food and Drug Administration(FDA), in combination with cationic
transfection agents suchas poly-L-lysine or the FDA-approved agent, protamine
sulfate,can safely and effectively label cells.
3. Functionalized Nanoparticles for Brain Tumor Imaging and Treatment: A
multifunctional nanoparticlepolyethyleneglycol-chlorotoxinfluorophore (NPC-Cy5.5) is
capable of targeting gliomacells and is detectable by both MR imaging and
fluorescencemicroscopy.
Cell and molecular imaging are rapidly converging with the emerging impact of nanotechnology
on CNS imaging and therapy. Although currently PET imaging agents appear to be more
biochemically specific (ie, FDG-PET) and high-field MR imaging provides spatial resolution to
<100 µm.
Regenerative medicines
Regenerative medicine offer hope for patients suffering organ failure or other injuries in which
they have lost their body part. Regenerative nano medicine could be divided into two sub areas
1. Smart biomaterials: Reaserch efforts have moved from the development of the inert
polymer which mimic the biomechanical properties of native tissue to bioactive
materials which promote the tissue self-healing.
2. Advanced cell therapy: the concept of cell as living drugs has changed the vision of
tissue engineering and cell therapies. There are many potential forms of cell therapy
including:


Transplantation of stem cells that are autologous (from patient) or allogeneic
(from donor)



The transplantation of the fully differentiated function cells.

Chemical compounds for Nanomedicine :


low molecular weight self assembling amphiphiles



self assembling amphiphilic polymers



polymer and drug conjugates



water insoluble polymers/ cross-linked polymers



dendrimers



carbon nanotubes

Examples of Nanomedicine performing medical procedures:


Diagnostic nanomachines –Monitor the internal chemistry of the body. Mobile
nanorobots, equipped with wireless transmitters, could circulate in the blood and lymph
systems, and send out warnings when chemical imbalances occur or worsen.


Implanted nanotechnology- Nanomedicines could dispense drugs or hormones as needed
in people with chronic imbalance or deficiency states.



Artificial antibodies, artificial white and red blood cells.



NanoBots act as miniature surgeons.



Nanomedicines replicate themselves, or correct genetic deficiencies by altering or
replacing DNA.

NanoMedicines and their functions:
Polymer conjugates (duncan, 2006)
Biodegradable polymers containing entrapped drug can be placed in the body, and are used for
localized drug delivery and/or the controlled release of the drug.
For e.g. Small polymer rods (goserelin (Zoladex)) and polymer microparticles (leuprolide
(Leupron Depot)) made from polylactideco-glycolide-entrapping leutinizing hormone releasing
hormone (LHRH) analogues are common treatments for prostate cancer,as the polymer slowly
degrades,therapeutic levels of the anti-tumour peptide are maintained for up to 3 months.
Another biodegradable polymeric implant, carmustine (Gliadel), is used to treat brain cancer
(glioblastoma multiform). In this case, a biodegradable polyanhydride polymer is made into
small polymer discs containing the alkylating agent bis(2-chloroethyl)nitrosourea (BCNU).
These discs are placed into the brain following the surgical removal of the tumour, and thereafter
they slowly degrade to deliver the drug locally, therefore preventing tumour re-growth.
Anti Cancer Polymeric medicines (Cheng & Jianjun, 2007)
Polymers play important roles in the design of delivery nanocarriers for cancer therapies.
Polymeric nanocarriers with anticancer drugs conjugated or encapsulated,also known as
polymeric nanomedicines, form a variety of different architectures including polymer-drug
conjugates, micelles, nanospheres, nanogels, vesicles, and dendrimers . The existing challenge of
drug delivery is to design vehicles that can carry sufficient drugs, efficiently cross various
physiological barriers to reach disease sites, and cure diseases in a less toxic and sustained
manner.

Figure 1 Schematic illustration of various polymeric nanomedicine drug delivery system

Tumour-targeted nanomedicines (Lammers, Henink, & Storm, 2008)
Drug targeting systems are nanometre-sized carrier materials designed for improving the
biodistribution of systemically applied (chemo) therapeutics.
Passive drug targeting
Substantial extravasation of the nanomedicine-associated drug into the interstitial fluid at the
tumour site,exploiting the locally increased vascular permeability.
Characteristics of an ideal tumour-targeted nanomedicine
(1) Increase drug localisation in the tumour through:
(a) Passive targeting
(b) Active targeting
(2) Decrease drug localisation in sensitive, non-target tissues
(3) Ensure minimal drug leakage during transit to target
(4) Protect the drug from degradation and from premature clearance
(5) Retain the drug at the target site for the desired period of time
(6) Facilitate cellular uptake and intracellular trafficking
(7) Biocompatible and biodegradable

Figure 2 Examples of clinically used tumour-targeted nanomedicines.Liposomal bilayers
are depicted in grey, polymers and polymer-coatings in green, biodegradable linkers (for
releasing drugs and polymer coatings)in blue,
A) Intravenous injection of a low-molecular-weight (chemo) therapeutic agent, which is
often rapidly cleared from blood, only low levels of the drug accumulate in tumours and
in tumour cells,their localisation to certain healthy organs and tissues can be relatively
high.
B) Implementation of a passively targeted drug delivery system, due to enhanced
permeability and retention (EPR) effect, the accumulation of the active agent in tumours
and in tumour cells can be increased substantially.
C) Active drug targeting to internalization-prone cell surface receptors (over)expressed by
cancer cells generally intends to improve the cellular uptake of the nanomedicine
systems, and can be particularly useful for the intracellular delivery of macromolecular
drugs, such as DNA, siRNA and proteins.
D) Active drug targeting to receptors (over)expressed by angiogenic endothelial cells aims to
reduce blood supply to tumours, thereby depriving tumour cells from oxygen and
nutrients.
E) Stimuli-sensitive nanomedicines, such as Thermodox, can be activated (i.e., induced to
release their contents) by externally applied physical triggers, such as hyperthermia,
ultrasound, magnetic fields and light.
F) In cases in which tumours are easily accessible, for example during surgery,sustainedrelease delivery devices can be implanted or injected directly into (the irresectable parts
of the) tumours.
Active Drug targeting
Targeting ligands are attached to drugs and drug delivery systems to act as homing devices for
binding to receptor structures expressed at the target site. Hodgkin’s lymphoma, T-cell
lymphoma and acute myeloid leukaemia, respectively, have been successfully used for
delivering radionuclides (Zevalin), immunotoxins (Ontak) and antitumour antiobiotics
(Mylotarg) more selectively to tumour cells. Antibodies, antibody fragments and peptides have
also been used as targeting moieties for drug delivery systems.

Conclusion
1. Nanotechnology will radically change the way we diagnose, treat and prevent cancer.
2. Nano medicine for cancer has the ability to improve health care dramatically.
3. Current research is mostly in diagnostic tools, although there are many other application
of nanomaterial’s in medicine.
Bibliography
abel, J. (n.d.). Nanomedicine and cancer. Department of physics , USU.
Cheng, R. T., & Jianjun. (2007). Anticancer Polymeric Nanomedicines. polymer reviews , 345-381.
duncan, R. (2006). Polymer conjugates as anticancer . Nature , 688-701.
Eaton, M. Nanomedicine and Regenerative Medicine .
European Technology platform. (2006). Nanomedicine: Nanotechnology for health.
khanna, V. k. (2012). Targeted Delivery of Nanomedicines. ISRN pharmacology .
Lammers, T., Henink, W., & Storm, G. (2008). Tumour-targeted nanomedicines: principles and practice.
British Journal of cancer , 392-397.
Muldoon, L., Tratnyek, P., Christoforidis, G., Neuwelt, E., Zhang, M., Manninger, S., et al. (2005). Imaging
and Nanomedicine for Diagnosis and therapy in Central nervous system.
(2009). Roadmap in nanomedicine towrds in 2020.

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Nanomedicine

  • 2. Abstract |Nanotechnology is an emerging scientific field creating materials, devices and systems at the molecular level. By being able to work at the ultra-small scale( billionth of a metre), nanotechnology is being used to deliver innovations in sectors including health.Nanomedicine is the medical application of Nanoscience which ranges application of Nanomaterials to Nanoelectronic biosensors and even future applications of molecular technology. Around 130 nano-tech based drugs and delivery systems are been developed worldwide (Nature materials, April 2006) . Nanomedicine exploits the improved physical, chemical and biological properties of materials at the nanoscale, and offers the potential to enable early detection, prevention, improved diagnosis and imaging, treatment of diseases. Nanomedicine includes targeted delivery and regenerative medicine; it interfaces nanomaterials (surfaces, particles, etc) or analytical instruments with "living" human material (cells, tissue, body fluids).Nanomedicines are solution to some disease like Cancer, diabetics, cardiovascular diseases, multiple sclerosis, Alzheimer's and Parkinson's disease. Uses of NanoMedicine :  Targeted drug delivery  Diagnosis and Imaging  Regenerative medicines Targeted drug delivery Target drug delivery seeks to concentrate medicine to diseased cells/tissues and organs. This is in contrast to current drug delivery trends were a medication is generally administered through the blood supply resulting in only a small amount of the drug reaching the affected area. Another good example is Cancer treatment through chemotherapy, in which cancer effected cell are radiated ,but this cause severe damage to unaffected cells to reduce damaging of unaffected cells we directly target to the diseased cells by Nanomedicines.
  • 3. Diagnosis and Imaging (Muldoon, et al., 2005) NanoMedicine researchers seek to identify and cure life-threatening diseases at the earliest stage. Researchers are exploring ways for nanotechnology and imaging instruments to better analysis disease, while offering less painful and evasive methods to patients. Imaging is the strategies to identify the cancer type of diseases. The effected cell or part of the body show different color or different property than normal cells we can identify difference in diagnosis and imaging. It show dark spot. Quantum dot technique used to imaging the effected cells. The blood-brain barrier (BBB) presents a major obstacle to the treatment of malignant brain tumors and other central nervous system (CNS) diseases. Various imaging techniques: 1. PET Imaging of Gliomas:PET imaging can be helpful in differentiating low-grade gliomas,high-grade tumors, and radiation necrosis and allowsdetermination of important clinical parameters such as metabolism. 2. Tracking Magnetically Labeled Stem Cells:Various approaches have been developed using coated SPIO nanoparticles to magnetically label stem cells and other mammaliancells for cellular MR imaging.14 Ferumoxides, a SPIOapproved by the United States Food and Drug Administration(FDA), in combination with cationic transfection agents suchas poly-L-lysine or the FDA-approved agent, protamine sulfate,can safely and effectively label cells. 3. Functionalized Nanoparticles for Brain Tumor Imaging and Treatment: A multifunctional nanoparticlepolyethyleneglycol-chlorotoxinfluorophore (NPC-Cy5.5) is capable of targeting gliomacells and is detectable by both MR imaging and fluorescencemicroscopy. Cell and molecular imaging are rapidly converging with the emerging impact of nanotechnology on CNS imaging and therapy. Although currently PET imaging agents appear to be more biochemically specific (ie, FDG-PET) and high-field MR imaging provides spatial resolution to <100 µm.
  • 4. Regenerative medicines Regenerative medicine offer hope for patients suffering organ failure or other injuries in which they have lost their body part. Regenerative nano medicine could be divided into two sub areas 1. Smart biomaterials: Reaserch efforts have moved from the development of the inert polymer which mimic the biomechanical properties of native tissue to bioactive materials which promote the tissue self-healing. 2. Advanced cell therapy: the concept of cell as living drugs has changed the vision of tissue engineering and cell therapies. There are many potential forms of cell therapy including:  Transplantation of stem cells that are autologous (from patient) or allogeneic (from donor)  The transplantation of the fully differentiated function cells. Chemical compounds for Nanomedicine :  low molecular weight self assembling amphiphiles  self assembling amphiphilic polymers  polymer and drug conjugates  water insoluble polymers/ cross-linked polymers  dendrimers  carbon nanotubes Examples of Nanomedicine performing medical procedures:  Diagnostic nanomachines –Monitor the internal chemistry of the body. Mobile nanorobots, equipped with wireless transmitters, could circulate in the blood and lymph systems, and send out warnings when chemical imbalances occur or worsen.
  • 5.  Implanted nanotechnology- Nanomedicines could dispense drugs or hormones as needed in people with chronic imbalance or deficiency states.  Artificial antibodies, artificial white and red blood cells.  NanoBots act as miniature surgeons.  Nanomedicines replicate themselves, or correct genetic deficiencies by altering or replacing DNA. NanoMedicines and their functions: Polymer conjugates (duncan, 2006) Biodegradable polymers containing entrapped drug can be placed in the body, and are used for localized drug delivery and/or the controlled release of the drug. For e.g. Small polymer rods (goserelin (Zoladex)) and polymer microparticles (leuprolide (Leupron Depot)) made from polylactideco-glycolide-entrapping leutinizing hormone releasing hormone (LHRH) analogues are common treatments for prostate cancer,as the polymer slowly degrades,therapeutic levels of the anti-tumour peptide are maintained for up to 3 months. Another biodegradable polymeric implant, carmustine (Gliadel), is used to treat brain cancer (glioblastoma multiform). In this case, a biodegradable polyanhydride polymer is made into small polymer discs containing the alkylating agent bis(2-chloroethyl)nitrosourea (BCNU). These discs are placed into the brain following the surgical removal of the tumour, and thereafter they slowly degrade to deliver the drug locally, therefore preventing tumour re-growth. Anti Cancer Polymeric medicines (Cheng & Jianjun, 2007) Polymers play important roles in the design of delivery nanocarriers for cancer therapies. Polymeric nanocarriers with anticancer drugs conjugated or encapsulated,also known as polymeric nanomedicines, form a variety of different architectures including polymer-drug conjugates, micelles, nanospheres, nanogels, vesicles, and dendrimers . The existing challenge of drug delivery is to design vehicles that can carry sufficient drugs, efficiently cross various
  • 6. physiological barriers to reach disease sites, and cure diseases in a less toxic and sustained manner. Figure 1 Schematic illustration of various polymeric nanomedicine drug delivery system Tumour-targeted nanomedicines (Lammers, Henink, & Storm, 2008) Drug targeting systems are nanometre-sized carrier materials designed for improving the biodistribution of systemically applied (chemo) therapeutics. Passive drug targeting Substantial extravasation of the nanomedicine-associated drug into the interstitial fluid at the tumour site,exploiting the locally increased vascular permeability. Characteristics of an ideal tumour-targeted nanomedicine
  • 7. (1) Increase drug localisation in the tumour through: (a) Passive targeting (b) Active targeting (2) Decrease drug localisation in sensitive, non-target tissues (3) Ensure minimal drug leakage during transit to target (4) Protect the drug from degradation and from premature clearance (5) Retain the drug at the target site for the desired period of time (6) Facilitate cellular uptake and intracellular trafficking (7) Biocompatible and biodegradable Figure 2 Examples of clinically used tumour-targeted nanomedicines.Liposomal bilayers are depicted in grey, polymers and polymer-coatings in green, biodegradable linkers (for releasing drugs and polymer coatings)in blue,
  • 8. A) Intravenous injection of a low-molecular-weight (chemo) therapeutic agent, which is often rapidly cleared from blood, only low levels of the drug accumulate in tumours and in tumour cells,their localisation to certain healthy organs and tissues can be relatively high. B) Implementation of a passively targeted drug delivery system, due to enhanced permeability and retention (EPR) effect, the accumulation of the active agent in tumours and in tumour cells can be increased substantially. C) Active drug targeting to internalization-prone cell surface receptors (over)expressed by cancer cells generally intends to improve the cellular uptake of the nanomedicine systems, and can be particularly useful for the intracellular delivery of macromolecular drugs, such as DNA, siRNA and proteins. D) Active drug targeting to receptors (over)expressed by angiogenic endothelial cells aims to reduce blood supply to tumours, thereby depriving tumour cells from oxygen and nutrients.
  • 9. E) Stimuli-sensitive nanomedicines, such as Thermodox, can be activated (i.e., induced to release their contents) by externally applied physical triggers, such as hyperthermia, ultrasound, magnetic fields and light. F) In cases in which tumours are easily accessible, for example during surgery,sustainedrelease delivery devices can be implanted or injected directly into (the irresectable parts of the) tumours. Active Drug targeting Targeting ligands are attached to drugs and drug delivery systems to act as homing devices for binding to receptor structures expressed at the target site. Hodgkin’s lymphoma, T-cell lymphoma and acute myeloid leukaemia, respectively, have been successfully used for delivering radionuclides (Zevalin), immunotoxins (Ontak) and antitumour antiobiotics (Mylotarg) more selectively to tumour cells. Antibodies, antibody fragments and peptides have also been used as targeting moieties for drug delivery systems. Conclusion 1. Nanotechnology will radically change the way we diagnose, treat and prevent cancer. 2. Nano medicine for cancer has the ability to improve health care dramatically. 3. Current research is mostly in diagnostic tools, although there are many other application of nanomaterial’s in medicine.
  • 10. Bibliography abel, J. (n.d.). Nanomedicine and cancer. Department of physics , USU. Cheng, R. T., & Jianjun. (2007). Anticancer Polymeric Nanomedicines. polymer reviews , 345-381. duncan, R. (2006). Polymer conjugates as anticancer . Nature , 688-701. Eaton, M. Nanomedicine and Regenerative Medicine . European Technology platform. (2006). Nanomedicine: Nanotechnology for health. khanna, V. k. (2012). Targeted Delivery of Nanomedicines. ISRN pharmacology . Lammers, T., Henink, W., & Storm, G. (2008). Tumour-targeted nanomedicines: principles and practice. British Journal of cancer , 392-397. Muldoon, L., Tratnyek, P., Christoforidis, G., Neuwelt, E., Zhang, M., Manninger, S., et al. (2005). Imaging and Nanomedicine for Diagnosis and therapy in Central nervous system. (2009). Roadmap in nanomedicine towrds in 2020.