Theranostics IV Flashcards
Theranostics
Imaging
• MRI
• Fluorescence
• Ultrasound
Therapy
• Hyperthermia
• Drug release
• Free radical production
Metallic nanoparticles
- Metal nanoparticles possess previously- unexpected benefits with application in both the conventional technology and experimental medical industries
- These nanostructured metals (and derivatives) are typically formed via reduction of metal salts
- Common metallic nanoparticles include gold, silver, copper, zinc, iron oxide etc
- In electronics manufacturing it has been found that thin films of extra-small copper particles exhibit a peculiarly strong electrocatalytic behaviour, making them prime candidates for many types of electric processes
- In the biomedical and pharmaceutical fields their vast potential is only now being realised
Gold nanoparticles
• Gold nanoparticles are also known as “colloidal gold” or sometimes “nano-gold.”
• When colloidal gold is suspended in a fluid (usually water) the solution colour is dependant on nanoparticle size.
• If the gold particles are extremely small (~2nm), the liquid appears to be an intense shade of red, as the size
increases up to 50nm the solution changes to a violet colour.
Gold nanoparticles can form in many different geometries, depending on the processincluding rods, cubes, shells* and spheres etc.
*Gold nanoshells difficult to visualise with transmission electron microscopy, appears as a particle
Colloidal Gold Applications
- Colloidal gold has been around since ancient originally used to stain glass.
- Nowadays, gold nanoparticles are highly useful for a wide range of processes including general nanotechnology, electronics manufacturing, the synthesizing of rare materials .
- Colloidal gold is also extremely useful in the biomedical field.
Biomedical Applications of gold nanoparticles
- Clinical studies show that injecting gold nanoparticles can relieve many symptoms of rheumatoid arthritis.
- Gold nanoparticles may also provide the cure for Alzheimer’s.
- This terrible disease ravages the human brain with a buildup of plaque and betay-amyloid fibrils which affect our motor skills and memory functions, among others.
- Scientists have discovered that a combination of colloidal gold and microwave radiation can destroy these harmful plaques and fibrils, allowing the brain to heal itself and resume normal functions
Optical properties of gold nanoparticles
- Gold is renowned for its chemical stability, biocompatibility along with unique surface plasmon resonance (SPR) properties in the nanoshell structure
- This SPR quality allows gold to strongly absorb and scatter visible and near infrared (NIR) light at a peak wavelengths determined by the particle or shell diameter/shell thickness ratio
- By exploitation of the SPR effect gold particles/shells absorb visible/NIR wavelengths resulting in an increase in temperature
- At NIR wavelengths, in physiological conditions optical transmission is optimal i.e. light at NIR wavelengths travels uninterrupted through body tissue
- As a result colloidal gold irradiated with NIR light can act as ‘nanoheaters’ resulting in cell hyperthermia
- As such tumour cells can be completely ablated
- Gold nanoshells have proven to be more effective as nano heaters than nanoparticles
Gold shells can be easily surface funtionalised via chemical modification using polymers or targeting molecules possessing thiol (-SH) groups which are strongly adsorbed onto the gold surface
Iron oxide nanoparticles
- Magnetic iron oxide nanoparticles (MNPs) have become widely studied for biomedical applications in recent years
- These applications include detection at the cellular level, imaging using magnetic resonance imaging (MRI), targeted drug delivery and gene therapy
- The biological application of any particulate system is dependent on its biocompatibility and stability in aqueous environment
- MNPs aggregate easily in solution due to their inherent magnetic nature
- This undesirable problem can be overcome by surface engineering of the particles with coatings such as silica and polymers
Alloy nanoparticles
- Iron platinum nanoparticles are currently under investigation
- Particles benefit from magnetic properties
- Platinum exhibits anti-tumoral effects
- Effect already exploited clinically in drugs such as CISplatin etc
Alloy nanoparticles Applications
• Antitumoral therapeutic
- MRI contrast agent
- Used for image guided therapies
Quantum dots
- Luminescent nanoparticulates
- Primary application: optical and electronic devices, chemical sensors, light emitting diodes
- Recently exploited for biomedical purposes
- Fluorescent tagging used in immunoassays, cellular labelling, tissue imaging etc
Quantum dots Properties
- Small size: 2-10nm
- Used for labelling larger nanoparticulates
- Versitile surface chemistry
- Use of dots as traceable analogues of other nanocarriers
- Narrow emission profile
- Simultaneous observation of multiple NP carriers in same model system
- High brightness
- Study of individual nanocarriers in intracellular trafficking
- High photostability
- Real time monitoring
- Sensitivity to microenvironment
- Monitoring changes in local microenvironments during stages of trafficking
Hybrid nanoparticles
• Detection at the cellular level
• Imaging using magnetic resonance imaging (MRI)
• Targeted drug delivery and gene therapy.
• Chemically stable
• Biocompatibility
• Surface plasmon resonance (SPR) SPR allowing strong
absorption and scatter at visible and near infrared wavelengths upon irradiation resulting in heating effect.
Hybrid Nanoparticle uses
Targetted therapy
Drug delivery
Cell sorting
MRI contrast agent
Biological detection
Multifunctional theranostic agent
HNPs for pancreatic cancer therapy
Type 1 - Exploited as ‘nano’heater for cellular hyperthermia
Type 2 - Surface functionalised with drug and
targeting molecules via thermosensitive linkers
- Upon heating thermosensitive bonds break and drug molecules released
Uses: Water soluble drugs
Type 3 - Incorporated into other drug delivery systems such as amphiphilic polymers, dendrimers, liposomes etc.
- Upon heating micelle disrupts and drug molecules released
Uses: Insoluble drugs (60% of all drugs under development)
Pancreatic cancer
- 4th most common cause of cancer-related death in the Western world
- Non-specificity of symptoms
- Advanced disease at presentation
- Lack of effective adjuvant and systemic therapy
- Gemcitabine only chemotherapy available clinically
- Only effective in 23.8% (poor drug penetration)
- Only alternative being surgical removal of the localized tumour
