nanotechnology on biomedical applications
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Nanotechnology on biomedical applicationsTRANSCRIPT
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Nanotechnology in Biomedical Applications
By: Gondesi Anil Kumar Reddy 11D110048
INDIAN INSTITUTE OF TECHNOLOGY BOMBAY Department of Metallurgical Engineering & Materials Science
MM 396: B.Tech. Credit Seminar Supervisor: Prof. D Bahadur
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Nanoparticles For Cancer Therapy
� Thermotherapy
� Photodynamic therapy
� Chemotherapy
� Radiotherapy
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Photodynamic Therapy
What is Photodynamic Therapy?
� Treatment that uses a drug, called a photosensitizer or photosensitizing agent, and a particular type of light.
� When photosensitizers are exposed to a specific wavelength of light, they produce a form of oxygen that kills nearby cells.
� Each photosensitizer is activated by light of a specific wavelength.
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Photodynamic Therapy
How is PDT used to treat cancer?
• A photosensitizing agent is injected into the bloodstream.
• Approx. 24 to 72 hours after injection, when most of the agent has left normal cells but remains in cancer cells, the tumor is exposed to light
• The photosensitizer in the tumor absorbs the light and produces an active form of oxygen that destroys nearby cancer cells
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Photodynamic Therapy
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Photodynamic Therapy
In addition to directly killing cancer cells, PDT appears to destroy tumors in two other ways:
� damage blood vessels in the tumor, thereby preventing the cancer from receiving necessary nutrients.
� PDT also may activate the immune system to attack the tumor cells.
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Photodynamic Therapy
Light Sources:
� Laser: Directed through fiber optic cables to deliver light to areas inside the body. Ex: a fiber optic cable can be inserted through an endoscope into the lungs or esophagus to treat cancer in these organs.
� Other sources include, Light-emitting diodes (LEDs) : Used for surface tumors, such as skin cancer.
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Photodynamic Therapy
Extracorporeal photopheresis (ECP):
� Outpatient procedure.
� A machine is used to collect the patient’s blood cells,
� Treat them outside the body with photosensitizing agent,
� Expose them to light, and then return them to the patient.
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Photodynamic Therapy
Types of cancer are currently treated with PDT:
� Esophageal cancer
� Precancerous lesions in patients with Barrett esophagus
� Non-small cell lung cancer
Photosensitizing agent called porfimer sodium, or Photofrin®
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Photodynamic Therapy
Quantum dots as photosensitisers and carriers :
� Optical properties can be tuned to absorb and emit in the near-infrared region of the spectrum by changing their size and composition.
� The surface coating of quantum dots can be functionalised to make them more water soluble and biocompatible
� Act as photosensitiser alone generating reactive singlet oxygen as well as promote the effect of classical photosensitisers linked to quantum dots
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Photodynamic Therapy
Quantum dots as photosensitisers :
� Excites
� Energy transfer
to triplet oxygen
� Generate radical oxygen species (ROS)
� ROS cause cytotoxic reactions in cells via apoptosis
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Photodynamic Therapy
Quantum dots as carriers :
� Excites
� Energy transfer
to classical photosensitiser
� Via fluorescence resonance energy transfer (FRET) to triplet oxygen producing singlet oxygen
� Singlet oxygen cause cytotoxic reactions in cells via apoptosis
FRET is a distance-dependent interaction between the electronic excited states of two dye molecules in which excitation is transferred from a donor molecule to an acceptor molecule without emission of a photon.
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Photodynamic Therapy
Ceramic-based nanoparticles as carriers :
� Act as delivery system for photosensitiser agents
� Silica-based np’s (30nm) doped with water-insoluble photosensitisers are taken up into the cytosol of tumour cells and generate singlet oxygen
� Size of the np is important because the lifetime of singlet in aqueous media is in microsec domain, during which interval it can diffuse over a radial distance of at least 100 nm
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Photodynamic Therapy
Nanoplatforms based on nanocomposite particles :
� A magnetic core of γ-Fe2O3 can be embedded within silica-based nanospheres functionalised with a targeting agent
� Applying a DC magnetic field results in a selective magnetocytolysis of targeted cells only
� DC magnetic fields can be generated by medical magnetic resonance imaging devices
� Development of nanoplatform with “dual lethality” combining the photocytotoxic effect of the photosensitiser with the magnetocytolytic property are also in progress.
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Photodynamic Therapy
Limitations:
� Light needed to activate most photosensitizers cannot pass through more than about one-third of an inch of tissue .
� Porfimer sodium makes the skin and eyes sensitive to light for approximately 6 weeks after treatment.
� Cause burns, swelling, pain, and scarring in nearby healthy tissue
� Coughing, trouble swallowing, stomach pain, painful breathing, or shortness of breath
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Photodynamic Therapy
Future Scope:
� Brain, skin, prostate, cervix, and peritoneal cavity cancer
� Research on the development of photosensitizers that are more powerful
� Investigating ways to improve equipment and the delivery of the activating light.
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Chemotherapy
� Chemotherapy uses medications which target and destroy cells that are rapidly dividing
� Cancer cells are more sensitive to chemotherapy than healthy cells because they divide more frequently
� Healthy cells can also be affected by chemotherapy, especially the rapidly dividing cells of the skin, hair, lining of the stomach, intestines, the bladder, and the bone marrow
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Chemotherapy
Nano-structured polymer capsules:
� Used to deliver chemotherapy directly to tumours, leaving adjacent tissue intact
v Capsule: • Templating core (~1μm), which
contains drug particles • Surrounded by multi-layered
polymer spheres with embedded light-absorbing gold nanoparticles (~6nm)
• A lipid bilayer and tumour-specific antibodies form an outer layer.
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Chemotherapy
• Injected into blood and concentrated into tumours • A 10 nanosec low- energy pulse from a near-infrared laser is
applied, sufficient to heat the gold np’s • Gold nanoparticles which swell up to 50 nm in diameter • Will melt the gold, rupture the polymer spheres and the nano-
structured capsules will subsequently release their contents
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Chemotherapy
Nanocells:
� Fundamental challenges in cancer chemotherapy are its toxicity to healthy cells and drug resistance by cancer cells
� In cancer therapy, anti-angiogenesis therapy is an elegant concept based on the starvation of tumour cell by impairment of blood supply
� However, lack of oxygen prompt tumour cells to release a cell signaling molecule known as hypoxia-inducible factor-1α , which triggers metastasis and the development of resistance to further chemotherapy
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Chemotherapy
� Solution: combining chemotherapy and anti- angiogenesis
� Problem again: inherent engineering problem
1. Long- term shutdown of tumour blood vessels by an anti-angiogenesis agent can prevent the tumour from receiving a chemotherapy agent
2. The two drugs behave differently and are delivered on different schedules: anti-angiogenics over a prolonged period and chemotherapy in cycles
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Chemotherapy
Solution: Nanocell
� Dual-chamber, double-acting, drug-packing
� Effective and safe, with prolonged survival, against two distinct forms of cancers, i.e. melanoma and Lewis lung cancer, in mice
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Chemotherapy
Structure: (a balloon within a balloon)
� Outer membrane: made of pegylated-phospholipid block-copolymer, was loaded with the anti-angiogenic drug combrestastatin
� The inner balloon: composed of the biodegradable and nonbioactive poly-lactic-co-glycolic acid, was loaded with the chemotherapy agent doxorubicin.
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Chemotherapy
Functions:
� Pegylation of outer membrane creates "stealth" surface chemistry that allows the nanocells to evade the immune system
� The size of the nanocells allows tumour cells to take them up preferentially compared to other (healthy) cells.
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Chemotherapy Working:
� Nanocell goes inside the tumour and its outer membrane disintegrates, rapidly deploying the anti-angiogenic drug
� The blood vessels feeding the tumour then collapse trapping the loaded nanoparticle in the tumour, where it slowly releases the chemotherapeutic agent
� The nanocell works better against melanoma than lung cancer, indicating the need to systematically evaluate drug combinations and loading mechanisms for different cancers.
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Radiotherapy
� Radiotherapy is a treatment for cancer using high -energy radiation, usually X-rays
� The type and amount of radiation that you receive is carefully calculated to damage the cancer cells, which are abnormal cells
� This stops the cells from dividing properly and as a result they are destroyed.
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Radiotherapy
Dendrimers for boron neutron capture therapy :
� Boron neutron capture therapy: which is an experimental approach to cancer treatment using a two-step process
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Radiotherapy
Two step:
1. Patient is injected with a non-radioactive pharmaceutical which selectively migrates to cancer cells. This component contains a stable isotope of boron (10B)
2. The patient is irradiated by a neutron beam of low-energy or thermal neutrons
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Radiotherapy
Working:
� Neutrons in the beam interact with the boron in the tumour causing the boron atom to split into an alpha particle (high-energy helium-4 nucleus) and a lithium-7 ion
� Both of these particles have a very short range and destroy tumour cells in which it is contained
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Radiotherapy
Carbon nanotubes for boron neutron capture therapy:
� Recently, water-soluble SWCNTs with appended C2B9 units have been shown to be promising nanovehicles for boron delivery to tumour cells
� Tumour tissue shows enhanced accululation and retention of these modified SWCNTs
� The actual mechanism of acculumation has not yet been determined
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Radiotherapy
Gold nanoparticles :
� Intravenous injection of gold nanoparticles (~2 nm in diameter) can enhance radiotherapy (X- rays)
� Results in eradication of subcutaneous mammary tumours in mice .
� One-year survival is 86% versus 20% with X-rays alone.
� Apparently, gold nanoparticles are non-toxic to mice and are cleared from the body through the kidneys.