Cellular Nanotechnology Exam 1

physical vapor deposition (PVD)

• occurs in vacuum chamber

• generation of vapor gas via either evaporation, sputter, or laser ablation

sputtering

• technique used in PVD

• preferred if wanting multicomponent film

• atoms ejected from target surface by impact of energetic ions

• capable of depositing high melting point materials

• sputter-grown films have higher density due to sputtered atoms having higher energy

• disadvantage: more prone to contamination due to lower purity of sputtered target materials

evaporation

• technique used in PVD

• involves removing atoms from a source, usually by heating above melting point

• preferred over sputtering if purity matters

• disadvantages: limitation in multicomponent materials

PVD disadvantages

• high cost

• need for vacuum and high temperatures

• requires cooling systems

Titanium and alloys

• Excellent biocompatibility

• corrosion resistance

• low modulus of elasticity similar to bone

• good mechanical properties

• Cons: poor wear resistance compared to other materials, potential release of metallic ions, limitations in promoting direct bone bonding

hydroxyapatite

• Bioactive ceramic that closely resembles the mineral component of bones

• Provide biocompatible surface that promotes osseointegration by facilitating the formation of a bond between the implant and surrounding bone tissue

• Cons: brittle nature may limit use in load-bearing applications, challenges in achieving strong adhesion to substrate due to differences in thermal expansion

Zirconium and alloys

• Good biocompatibility and low toxicity

• Enhance wear resistance and promote cell adhesion

• Cons: limited availability of __-specific coatings, potential challenges in achieving uniform coatings due to high melting point

Chemical Vapor Deposition (CVD)

• Process where gaseous precursors react to form a solid coating on a heating substrate

• Used to apply solid thin film coating to a surface but also used to produce high purity bulk materials and powders

• In typical ___, the wafer (substrate) is exposed to one or more volatile precursor, which react and/or decompose on the substrate surface to produce the desired deposit. Frequently, volatile by-products are also produced, which are removed by gas flow through the reaction chamber

CVD Steps

1. Transportation

2. Absorption

3. Surface reaction with gas precursors

4. Surface diffusion

5. Nucleation and growth of films

6. Deposition of gaseous precursor atoms

CVD Advantages

• High pure dense film

• Coating complex shapes

• Producing metals, ceramics

Sol-gel

• In this technique a colloidal suspension (Sol), is generated which is then converted to a viscous gel. The sol–gel processing method has been in use for many years for producing metal oxide and ceramic powders with high purity and high homogeneity. In the process, reactive metal precursors were initially hydrolysed, followed by condensation and polymerization reactions.

• Done at room temperature

• Used for producing metal oxide and ceramic powders

Sol-gel coating requirements

• pure coating (impurity will cause side effects)

• room temperature (substrate will be melted at high temperature)

• complex shape (Implant has a complex shape)

• Therefore ___ will be the best way to produce such a coating

Sol-gel steps

• Substrate preparation: cleaning, surface modification to enhance adhesion.

• Sol preparation: mixing precursor compounds, controlling sol viscosity.

• Deposition: methods include dipping, spinning, spraying, and brushing.

• Gelation: hydrolysis and condensation reactions leading to the formation of a gel network.

• Drying and curing: removal of solvent and formation of a solid film.

Biosafety hazards

• blue: health hazard

• red: fire hazard

• yellow: instability hazard

• white: specific hazard (acid, alkali, corrosive, oxidizer, etc.)

• scale of 1 to 4 with 4 being worst, 0 = no hazard/stable

Wet chemical oxidation/reduction

• Reducing agent (The reducing agent will lose electrons to the target ions. The ions will get reduced to atoms, which develops NPs.)

• Converts metal ions from a precursor into metallic NPs

• Advantages: versatility, scalability, and control over nanoparticle properties

Common reducing agents

• sodium borohydride

• sodium citrate

Needed for wet chemical oxidation/reduction

1. the salt form of the metal

2. reducing agents

3. stabilizing agents (Cover the particle surface & prevent aggregation)

4. Capping agent (regulate the growth and particle size)

Citrate Route

• most common technique for colloidal gold NPs

• mean diameter of 15 nm

• Sodium citrate (amino acids also successful) acts as stabilizing agent, reducing Au3+ ions to atoms and subsequent aggregation results in the formations of NPs at elevated temperature.

biological synthesis of gold NPs

• Utilizes plants, bacteria, fungi, or biomolecules (enzymes, proteins, polysaccharides) as eco-friendly reducing and stabilizing agents

biological synthesis of silver NPs procedure

• Extract bioactive compounds from the biological source.

• Mix the extract with a gold salt solution.

• The reducing agents present in the extract reduce gold ions to form nanoparticles.

• The capping agents naturally present in the extract can stabilize the nanoparticles.

Surface Plasmon Resonance (SPR)

• collective oscillation of free electrons in a metal in response to incident light.

• this resonance occurs at a specific wavelength, resulting in enhanced electromagnetic fields around the nanoparticle's surface

SPR in imaging

• gold nanoparticles allow the expression of an intense color when exposed to light that can be tuned by altering size, shape composition and coupling

• enhance other optical signals such as fluorescence and Raman scattering making them suitable for biosensors development. Localization of electromagnetic field results in amplification of ___ signals and surface enhanced raman scattering.

• When chemical reactions happen between molecules and GNPs a high molar and significant color change can be observed by aggregation of GNPs

• ___ effect will change when the size is nanoscale, resulting in confined localized ___

Superparamagnetism

• occurs in nanoparticles, particularly those below a critical size (typically < 20 nanometers for many materials)

• phenomenon where the magnetic moments of individual nanoparticles align with an external magnetic field, but they can reorient freely when the field is removed

• In bulk materials, this behavior is not observed.

• No retained magnetic field after magnetic removal

• Better escape of RES

Ferromagnetism

• iron, nickel, cobalt

• Magnetic moments tend to align in same direction resulting in a strong magnetic field

• Can retain magnetization even after external magnetic field is removed

• Atoms have permanent dipole moment, dipoles are oriented in same direction of the magnetic field

Why do you think Hyperthermia with MNPs is superior than other

hyperthermia techniques such as radio frequency?

• Provides localized therapy while sparing healthy tissue

• ___ can generate heat when exposed to an alternating magnetic field AKA hysteresis loss which can be used to selectively destroy cancer cells at temperatures above their tolerance

• Promising technique for cancer treatment as it provides localized therapy while sparing healthy tissue

• Non-invasive way to raise temperature

• _ can be visualized with MRI

• Can get functionalized with other type of treatment

Discuss why you think superparamagnetism will benefit drug delivery with magnetic nanoparticles?

• Do not retain magnetism after magnetic removal

• External magnetic field can precisely guide the superparamagnetic NPs to a specific target site in the body, allowing for localized drug release and reducing off-target effects

Why do you think using magnetic nanoparticles will enhance the contrast of MRI imaging?

• Magnetic nanoparticles, depending on their composition and surface properties, can influence both T1 and T2 relaxation times of nearby water protons in the tissue. T1 relaxation is related to the recovery of longitudinal magnetization, while T2 relaxation is associated with the decay of transverse magnetization. By affecting these relaxation times, magnetic nanoparticles can alter the signal intensity in MRI images.

• MNPs can be visualized with MRI

• Can serve as contrast agents, improving imaging of soft tissues

• Enhance visibility of specific anatomic structures and pathological changes

• Aid in early detection and monitoring of diseases, such as tumors and vascular abnormalities

Local magnetic field disturbances

• enhance contrast of MRI imaging

• Magnetic nanoparticles create local magnetic field disturbances in their vicinity

• Can lead to changes in the precession frequency of nearby water protons

• Altered precession frequency contributes to variations in the MR signal, resulting in contrast differences in the image

With the knowledge you gained from self-assembling peptides, design a sequence of amino acids that will have hydrogelation function can deliver anticancer drugs to tumor cells. Note that in cancer therapy a combination of anticancer drugs and anti-inflammatory drugs are often used. Also keep in mind adding amino acids with controlled release and targeting functions

• Anti-inflammatory: dexamethasone

• Amino acids that have controlled release

• Anti-cancer: doxorubicin (DXR), paclitaxel (Taxol)

• Self-assembly: dox/dex - cleaver/linker

• Self-assembled peptides: Di-phyenylalanine (FF)

• Used in 3D cell culture, drug delivery, bioimaging

• Fmoc protected FF will make hydrogels

• Can be loaded with anti-cancer drugs

• Examples: Fmoc-FF, Nap-FF, KLD, RADA, (EAEA)16

Dex-FF-(Taxol)-S-S-EE-RGD

• Dex: anti-inflammatory

• Taxol: anti-cancer

• S-S (disulfide bond): redox sensitive linker

  • Remains stable in bloodstream but breaks in reductive environment inside cells, triggering drug release

• EE (glutamic acid dipeptide/Glu-Glu): assembly

  • Used to improve solubility or provide additional sites for conjugation

• RDG (Arg-Gly-Asp peptide): cell adhesion

  • Enhances selective uptake by cancer cells

Magnetic targeted drug delivery

• __ can be functionalized with drug molecules and guided to specific target sites in the body using an external magnetic field.

• This approach minimizes systemic drug exposure and reduces side effects.

• It is particularly valuable in treating diseases like cancer, where precise drug delivery to tumor sites is critical.

Magnetic hyperthermia therapy

• Magnetic nanoparticles can generate heat when exposed to an alternating magnetic field, a phenomenon known as hysteresis loss.

• This heat can be used to selectively destroy cancer cells at temperatures above their tolerance.

• Magnetic hyperthermia is a promising technique for cancer treatment, as it provides localized therapy while sparing healthy tissue.

Vapor-Liquid-Solid

• widely used process for synthesizing carbon nanostructures, particularly carbon nanotubes (CNTs). It's a versatile method that allows for the

  controlled growth of nanostructures with well-defined properties.

• key steps: vapor phase, catalyst particles, adsorption and dissolution

Vapor phase

• first key step in VLS

• Precursor Gas: The process begins with a precursor gas containing carbon atoms. Common precursor gases include hydrocarbons like methane (CH4) or carbon monoxide (CO).

• Carrier Gas: A carrier gas, often an inert gas like hydrogen (H2), is introduced to transport the precursor gas to the reaction zone.

Catalyst Particles

• second key step in VLS

• A catalyst material, typically transition metals like iron (Fe), nickel (Ni), or cobalt (Co), is introduced into the reaction chamber.

• catalyst forms small droplets or nanoparticles due to the high temperature.

Adsorption and dissolution

• third key step of VLS

• Carbon atoms from the precursor gas adsorb onto the surface of the catalyst nanoparticles and dissolve into the metal.

• Essential for the subsequent growth of carbon nanostructures.

armchair

• CNT chirality classification

• have same chirality indices (n, n), where ‘n’ is an integer

• exhibit metallic properties which make them excellent conductors of electricity

zigzag

• CNT chirality classification

• chirality indices (n, 0), where ‘n’ is an integer

• can be either metallic or semiconducting depending on value of ‘n’