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Metallic nanoparticles final
- 1. Metallic nanoparticles Dr. MaryamGhanbari Islamic Azad University
- 2. Abstract • Metallic nanoparticleshave fascinated scientist for over a century and are now heavily utilized in biomedical sciences and engineering. • They are a focus of interest because of their huge potential in nanotechnology. • Metallic nanoparticles can be synthesized and modified with various chemical functional groups which allow them to be conjugated with antibodies, ligands, and drugs • Therefore, opening a wide range of applications in biotechnology, magnetic separation, and concentration of target analytes and vehicles for gene and drug delivery and more importantly diagnostic imaging.
- 4. • Various imagingmodalities have been developed: MRI, CT, PET, ultrasound, SERS, and optical imaging as an aid to image various disease states. • These are differ in both techniques and instrumentation and more importantly require a contrast agent with unique physiochemical properties. • This led to the invention of various nanoparticulated contrast agent such as: magnetic nanoparticles (Fe3O4), gold, and silver nanoparticles for their application in these imaging modalities. • In this section, we aim to provide an introduction to magnetic nanoparticles (Fe3O4), gold nanoparticles, nanoshells and nanocages, and silver nanoparticles followed by their synthesis, physiochemical properties, and applications in the diagnostic imaging and therapy of cancer.
- 5. excellent properties ofMetallic nanoparticles • Nanomaterials properties compared to their larger counterparts: • High surface-to-volume ratio. • Due to these unique properties, they make excellent candidate for biomedical applications
- 6. • In general,nanoparticles used in the field of biotechnology range in particle size between 10 and 500 nm, seldom exceeding 700 nm. • The nanosize of these particles allows various communications with biomolecules on the cell surfaces and within the cells • Its potential application in drug delivery system and noninvasive imaging offered various advantages over conventional pharmaceutical agents.
- 7. • it isimportant that the nanoparticulate systems should be stable, biocompatible, and selectively directed to specific sites in the body after systemic administration. • More specific targeting systems are designed to recognize the targeted cells such as cancer cells. This can be achieved by conjugating the nanoparticle with an appropriate ligand, which has a specific binding activity with respect to the target cells. • In addition, nanoparticles provide a platform to attach multiple copies of therapeutic substance on it and hence increase the concentration of therapeutic and diagnostic substances at the pathological site.
- 8. • the concentrationand dynamics of the active molecule can be varied by controlling the particle size of nanoparticles (>3–5 nm). • This control in particle size in conjugation with surface coating with ligand allows them to veil against body’s immune system, enabling them to circulate in the blood for longer period of time. • These advances in the field of biotechnology have opened an endless opportunities for molecular diagnostics and therapy.
- 9. • Targeted (activeor passive), these nanocarriers can be designed in a way to facilitate them to act as imaging probes using variety to techniques such as: • ultrasound (US), X-ray, computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), optical imaging, and surface-enhanced Raman imaging (SERS). • Hence, these so-called “molecular imaging probes” can noninvasively provide valuable information about differentiate abnormalities in various body structures and organs to determine the extent of disease, and evaluate the effectiveness of treatment. • Thus short molecular imaging enables the visualization of the cellular function and the follow-up of the molecular process in living organisms without perturbing them.
- 11. Enhanced Permeability andRetention (EPR) effect • The enhanced permeability and retention (EPR) effect is the mechanism by which high molecular weight non targeted drugs accumulate in tissues that offer increased vascular permeability, such as in sites of inflammation or cancer.
- 12. Active and Passivetargeting of nanoparticles • Passive targeting versus active targeting strategies for anticancer drug delivering system. • (Top) By the enhanced permeability and retention effect, nanoparticles (NPs) passively diffuse through the leaky vasculature and accumulate in tumor tissues. • In this case, drug may be released in the extracellular matrix and then diffuse through the tissue. • (Down) In active targeting, once particles have extravasated in the tumor tissue, the presence of targeting ligands (e.g., antibody, carbohydrate) on the NP surface facilitates their interaction with receptors that are present on tumor cells, resulting in enhanced accumulation and preferential cellular uptake through receptor mediated endocytosis
- 13. Iron Oxide Nanoparticles •Iron (III) oxide (Fe2O3) is a reddish brown, inorganic compound which is paramagnetic in nature and also one of the three main oxides of iron, while other two being FeO and Fe3O4. • Due to their ultrafine size, magnetic properties, and biocompatibility, superparamagnetic iron oxide nanoparticles (SPION) have emerged as promising candidates for various biomedical applications such as: enhanced resolution contrast agents for MRI targeted drug delivery and imaging hyperthermia gene therapy stem cell tracking molecular/cellular tracking magnetic separation technologies early detection of inflammatory, cancer, diabetes, and atherosclerosis
- 14. To understanding ofthe molecular biology of various diseases recommended the need of homogeneous and targeted imaging probes along with a narrow size distribution in between 10 and 250 nm in diameter. various chemical routes for synthesis of magnetic nanoparticles in this diameter range: sol–gel syntheses sonochemical reactions hydrothermal reactions hydrolysis and thermolysis of precursors flow injection syntheses electrospray syntheses However, the most common method for the production of magnetite nanoparticles is the chemical coprecipitation technique of iron salts.
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- 16. Coprecipitation: • Advantage ofthe coprecipitation : • large amount of nanoparticles can be synthesized but with limited control on size distribution. This is mainly due to that the kinetic factors are controlling the growth of the crystal. • Particulate magnetic contrast agents synthesized using these methods include: ultrasmall particles of iron oxide (USPIO) (10–40 nm) small particles of iron oxide (SPIO) (60–150 nm) • Monocrystalline USPIOs are also called as monocrystalline iron oxide nanoparticles (MIONs), whereas MIONs when cross-linked with dextran they are called crosslinked iron oxide nanoparticles CLIO
- 17. • The modificationof the dextran coating by carboxylation leads to a shorter clearance half-life in blood • A carboxyalkylated polysaccharide coated iron oxide nanoparticle, is already described as a good first-pass contrast agent • In order to improve the cellular uptake, these particles can be modified with a surface coating so that they can be easily conjugated to drugs, proteins, enzymes, antibodies, or nucleotides and can be directed to an organ, tissue, or tumor. • While traditional contrast agents distribute rather nonspecifically, targeted molecular imaging probes based on iron oxide nanoparticles have been developed that specifically target body tissue or cells
- 18. Structures of naturalpolysaccharides used for surface modification of MNPs
- 19. Schematic representation ofin vitro and in vivo gene delivery using magnetofection (grey color pattern on the left corner of the image represents the direction of movement of MNPs under the influence of magnet).
- 20. Some applications ofiron oxide nanoparticles in biomedical imaging A biocompatible iron oxide nanoprobe coated with poly ethylene glycol (PEG), which is capable of specifically targeting glioma tumors via the surface- bound targeting peptide. MRI studies showed the preferential accumulation of the nanoprobe within gliomas. • The further development and modification of the complexes of iron oxide along with dendrimers, polymeric nanoparticles, liposomes, and solid lipid nanoparticles are widely studied. • However, the toxicity of these magnetic nanoparticles to certain types of neuronal cells is still the matter of concern.
- 21. Superparamagnetic Iron OxideNanoparticles as MRI contrast agents for Non-invasive Stem Cell Labeling and Tracking
- 22. Gold Nanoparticles • Colloidalgold, also known as gold nanoparticles, is a suspension of nanometer-sized particles of gold. • The history of these colloidal solutions dates back to Roman times when they were used to stain glass for decorative purposes. • The modern scientific evaluation of colloidal gold did not begin until Michael Faraday’s work of the 1850s, when he observed that the colloidal gold solutions have properties that differ from the bulk gold. • Hence the colloidal solution is either an intense red color (for particles less than 100 nm) or a dirty yellowish color (for larger particles).
- 23. Applications of goldnanoparticles (AuNPs) • Diagnosis and treating of disease such as targeted chemotherapy and in pharmaceutical drug delivery due to their multifunctionality and unique characteristics. • AuNPs can be conjugated with ligands, imaging labels, therapeutic drugs and other functional moieties for site specific drug delivery application.
- 24. The characteristic propertiesfor gold nanoparticles • Small size (1–100 nm) and large surface-to-volume ratio • Unique physical and chemical properties that can be changed according to requirements of size, composition and shape • Quantitive and qualitative target-binding properties • Unique optical properties
- 25. Gold Nanoparticle opticalproperties • These optical properties are conferred by the interaction of light with electrons on the AuNP surface. • At a specific wavelength of light, collective oscillation of electrons on the AuNP surface cause a phenomenon called surface plasmon resonance (SPR), resulting in strong extinction of light (scattering and absorption). •
- 26. Cont… • The particularwavelength of light where this occurs is strongly dependant on the AuNP size, shape, surface and agglomeration state. • The influence of AuNP size on the surface plasmon resonance is affect the absorption maximum (λ max) which increases from 520nm to 570nm for 20nm and 100nm spherical AuNPs respectively. • In comparison, AuNPs with diameters below 2nm do not exhibit surface plasmon resonance.
- 27. • The rod-shapednanoparticles have two resonances: • one due to plasmon oscillation along the nanorod short axis and another due to plasmon oscillation along the long axis, which depends strongly on the nanorod aspect ratio (length- to-width ratio). The difference in color of the particle solutions is more dramatic for rods than for spheres. This is due to the nature of plasmon bands (one for spheres and two for rods) that are more sensitive to size for rods compared with spheres.
- 28. Photographs of aqueoussolutions of gold nanospheres as a function of increasing dimensions The size varies from 4 to 40 nm (TEMs a-e)
- 29. Photographs of aqueoussolutions of gold nanorods as a function of increasing dimensions The size varies from 1.3 to 5 nm for short rods (TEMs f-j) and 20 nm (TEM k) for long rods
- 30. synthesis of goldnanoparticles • The most prevalent method for the synthesis of monodisperse spherical gold nanoparticles was pioneered by Turkevich et al. in 1951. • This method uses the chemical reduction of gold salts such as hydrogen tetrachloroaurate (HAuCl4) using citrate as the reducing agent. • This method produces monodisperse spherical gold nanoparticles in the range of 10–20 nm in diameter. • The gold surface offers a unique opportunity to conjugate ligands such as oligonucleotides, proteins, and antibodies containing functional groups such as thiols, mercaptans, phosphines, and amines, which demonstrates a strong affinity for gold surface.
- 31. Examle of usinggold nanoparticles for cancer imaging • The use of gold nanoparticles for cancer imaging by selectively transporting AuNPs into the cancer cell nucleus. • Conjugat arginine–glycine–aspartic acid peptide (RGD) and a nuclear localization signal peptide (NLS) to a 30-nm AuNPs via PEG (poly ethylene glycol). • RGD is known to target αβ integrins receptors on the surface of the cell, whereas NLS sequence lysine–lysine–lysine–arginine–lysine (KKKRK) sequence is known to associate with importins in the cytoplasm, which enables the translocation to the nucleus. • The RGD-AuNPs specifically target the cytoplasm of cancer cells over that of normal cells, and the RGD/NLS-AuNPs specifically target the nuclei of cancer cells over those of normal cells.
- 32. The efficient uptakeof AuNPs in cancer cells compared with normal cells
- 33. Photodynamic therapy (PDT)of cancer • Photodynamic therapy (PDT) is a two-stage treatment that combines light energy with a drug (photosensitizer) designed to destroy cancerous cells after light activation. • Photosensitizers are activated usually by a laser. The photosensitizer is nontoxic until it is activated by light. However, after light activation, the photosensitizer becomes toxic to the targeted tissue. • Photosensitizers are molecules that can be activated by light in order to generate ROS that can damage cell structures from microorganisms or from diseased mammalian cells leading to cell death.
- 34. Reactive Oxygen Species(ROS) • ROS: An unavoidable consequence of aerobic metabolism is production of reactive oxygen species (ROS). • ROS include free radicals such as superoxide anion ( O 2 • − ), hydroxyl radical (•OH), as well as nonradical molecules like hydrogen peroxide (H2O2), singlet oxygen (1O2), and so forth.
- 35. Photothermal therapy (PTT)of cancer • The use of gold nanorods as photothermal agents. • Photothermal therapy (PTT) is a procedure in which a photosensitizer is excited with specific band light (mainly IR). • This activation brings the sensitizer to an excited state where it then releases vibrational energy in the form of heat. • The heat is the actual method of therapy that kills the targeted cells. • One of the biggest recent successes in photothermal therapy is the use of gold nanoparticles.
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- 38. • The rod-shapedgold nanoparticles with the absorption in the IR region, when selectively accumulated in tumors when bathed in laser light (in the IR region), the surrounding tissue is barely warmed, but the nanorods convert light to heat, killing the malignant cells.