Gold nanorods

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it gives information about the use of gold nanorods as phototherapeutic agents and drug delivery vehicles and the interactions and toxicity of the gold nanorods invivo

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Presented by: SK. Asma shaheda Gold Nanorods : Their potential for photothermal therapeutics and drug delivery, tempered by the complexity of their biological interactions

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1. Introduction: Nano technology has provided research level breakthroughs in biodiagnostics , drug delivery and cancer treatment. These breakthroughs start from physical size of ̴1-100nm nanoparticles made of organic or inorganic crystals. Nano particles possess EPR effects, that make them to accumulate in the tumour tissue to higher extents than in normal tissue due to leaky tumour blood vasculature. Nano particles – High surface area - Enhance drug’s solubility, stability and pharmacokinetic parameters - Requires only 1/100 th of normal dose - High local action and less side effects

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Classes of Nano particles: Organic – Polymers, dendrimers , solid-lipid nanoparticles Inorganic – Magnetic Iron oxide, quantum dots of various mineral compositions, silver, gold and silica Protein based – viruses and albumin GOLD?????? EPR effect High surface area Unique optical properties upon interaction with light such as strong absorption and scattering in the visible – near I.R region of electromagnetic spectrum, depending on size and shape Chemically inert

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a . Optical properties of Gold: Light absorption and scattering in “ Water Window” Gold shows the optical properties that absorb and emit light. Hence used in detection and destruction of tumour or other diseased tissue. Various methods based on the same principle are - Fiber optics - Solid state lasers and - Endoscopes Water window which lies at region ̴ 700-1200nm is widely considered to be the best spectral region for imaging and therapy. Gold nanorods are nearly ideal and preferentially absorb light at this region.

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Nano spheres absorb light at wavelength ~520nm and nanorods absorbs light at wavelength ~800nm. Absorption and scattering of wavelength by nanorods is sensitive to changes in dielectric constant of the surrounding medium around nanorods and to aggregation state of nanorods . This above property make nanorods chemically sensitive and hence these nanomaterials are used as “chemical sensors”. Compared to spheres rods are highly sensitive to changes in local dieletric constant. Hence used as - good contrasting agents. - in detection of cancerous cells when bound with antibodies

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b. Surface enhanced Raman spectroscopy: Light scattering depends on the absorption surface. Scattering will be elastic but after modifying the surface it will becomes inelastic. Nanorods produce effective SERS signals than spherical nanoparticles Hence used in diagnosis, imaging, and therapy. c. Photothermal effect: Nanoparticles release the absorbed energy in the form of heat that will results in increase in temperature ranging from ~10ºC -1000ºC. Temperature raise depends upon the - Laser power, time of irradiation and - Concentration of gold nanoparticles Temperature raise cause damage to pathogens, cultured cancer cells invitro and tumour tissue invivo .

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2. Synthesis of gold nanorods and surface modification: Using the seed-mediated approach, gold nanorods with different aspect ratios can be grown from pre-formed ~1.5–4 nm colloidal gold “seed” especially with the use of a low amount of additive ions such as silver. The final surface-bound molecules like quaternary ammonium surfactant molecules of cetyltrimethylammonium bromide (CTAB) are attached on gold nanorods using the wet chemical seed-mediated approach. CTAB promotes the growth of gold seeds in one dimension to produce Rods. As-prepared gold nanorods have a bilayer of CTAB, which provides the surface of nanorods with a positive effective surface charge and thus prevents the nanorods aggregation in water via electrostatic repulsion.

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The other methods for preparation of nanopartilces are - Electro-chemical synthesis - UV photochemical reduction of gold salts Layer by layer polyelectrolyte adsorption is an excellent technique that relies on sequential deposition of anionic and then cationic polyelectrolytes to the nanorod surface. This gives both cationic and anionic gold nanorods . Surfactant bilayer of CTAB on the surface of gold nanorods

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3. Gold nanorods as therapeutic agents: Gold nanorods themselves acts as drugs due to its photothermal effects. Wavelength Absorption for - Nanospheres at ~520nm and Nanorods at ~800nm Eg : 1. Gold nanorods bound with monoclonal antibodies specifically bound only to malignant epithelial cell lines and after irradiation continously , resulted in cell death at even low laser powers of 80mW. 2. 75% death of Psuedomonas aeruginosa with nanorods at 785nm at laser power of 50mW for 10min.

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4 . Gold nanorods as drug delivery vehicles : Show the following properties as drug delivery vehicles High drug entrapment target recognition low dose of drug Loading of drug plays a key role Drug release is by diffusion or enhanced by laser pulses that heat rod surface and thus initiate the drug release. Coating with hydrogel --- which are photoresponsive , release drug by swelling of gel upon irradiation.

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5. Interactions of gold nanorods : 3 types of interactions it show a. Gold nanorod - biological interactions b. Gold nanorod – cell interactions - cellular uptake - cellular toxicity c. Gold nanorod – organism interactions

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Interaction with biological media: When exposed to biological media, biomolecules adhere to surface of nanorods due to its large surface area Leads to protein corona It influences toxicity of nanorods , cellular uptake, and pharmacokinetics and immunogenecity of nanorods . Also leads to faster elimination during circulation by reticulo endothelial system. These interactions can be - detected by Isothermal titration calorimetry (ITC) or Gel electrophotesis and mass spectrophotometry . - prevented by addition of antifouling agents like PEG.

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b. Interactions with cells: Cellular uptake: - By Phagocytosis (larger) and receptor-mediated endocytosis (small) - Monitored by TEM - Analysed by digestion of cells and cellular fragments by strong acids to oxidize gold nanoparticles into gold ions. Cellular toxicity: 2 points must be studied under this -- Dose of nanorods sufficient to kill cells. -- mechanism of toxicity (toxicity is only due to ligands like CTAB) Invitro toxicity for cell lines, detected by initro -biochemical assays like general viability, oxidative stress and genetic toxicity assay.

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c . Interactions with organism: Study of properties of nanorods like - Pharmacological properties - which include interaction with blood, immune system and CVS or any major organs and - Pharmacokinetic properties like ADME Invivo studies……. - After I.V administration, within 30mins, CTAB gold nanorods were cleared from circulation and went to liver as 54% found in blood. - Mechanism is not clear about break down and excretion from body. - Chemical analysis of gold in tissues, did not observe any significant oxidative states of gold as other inorganic nanoparticles indicating that they are stable invivo .

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Conclusion: Gold nanorods are promising materials for drug delivery and photothermal therapy applications. Ease of synthesis, degree of size and shape and optical property control and ability to tune the surface chemistry favour them for biomedical applications Protein- interactions and its affect to cellular constituents must be studied in clear. Yet to be studied in detail about: Required therapeutic dose, toxic dose of nanorods purification processess of nanomaterials Long-term fate of nanorods in organism Long-term effects on organism upon gold nanorods exposure.

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References: Advanced drug delivery reviews 64 (2012), 190-199 Material science and engineering:R:Reports . Vol-65,issue 1-3. 15 May2009, pages 1-38 Target nanoparticles : An appealing drug delivery platform, Journal of nanomedicine and nanotechnology, March 2012. Surface enhanced Raman spectroscopy “Term paper for physics 598 OS”. Wikipedia

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