nanotechnology on biomedical applications

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

Nanoparticles For Cancer Therapy

� Thermotherapy

� Photodynamic therapy

� Chemotherapy

� Radiotherapy

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.


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


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.


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.


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.


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®


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


Quantum dots as photosensitisers :

�  Excites

�  Energy transfer

to triplet oxygen

�  Generate radical oxygen species (ROS)

�  ROS cause cytotoxic reactions in cells via apoptosis


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.


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


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.


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


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.

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

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.

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

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

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

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

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.

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.

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.

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.

Radiotherapy

Dendrimers for boron neutron capture therapy :

�  Boron neutron capture therapy: which is an experimental approach to cancer treatment using a two-step process

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

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

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

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.

nanotechnology on biomedical applications

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