Bme Nanotechnology Test 2

Front 1

Artificial Photosynthesis

Back 1

-Couple quantum dots with photoreaction center;
-creates a more efficient photon transfer
-absorbs 3x more photons from light with a quantum dot

Front 2

Examples of Quantum dots as drug carriers (2)

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Coat QD with PEG and drug molecule;
(1) captopril- antihypertensive drug (enzyme inhibitor)- efficiency didn't decrease;
(2) Naproxen- higher drug efficiency, good enzyme stability

Front 3

Quantum dots with sRNA

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sRNA- small RNA- double stranded therapeutic RNA molecules;
-to do this, covalently couple: QD--PEG--sRNA--target mol;
-interferes with RNA production & inhibits the protein synthesis;
-can monitor with real time evaluation

Front 4

Using QD to tag other nanocarriers: Liposomes

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Quantum dot associates with hydrophobic tails in liposome, can load them in immunoliposomes;
example: Liposome--PEG--NH2 ----> Liposome--PEG--NH--C=O--QD

Front 5

Using QD to tag other nanocarriers: Polymeric nanoparticles (2)

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(1) PLGA (poly(lactide-co-glycolide))- can look at uptake by different cells in vitro when you attach a QD to PLGA with a target molecule;

(2) PEG (Poly(ethylene glycol)) or PLA (poly(lactic acid))
- PEG--wheat germ agglutinum: targets brain cells and has an affinity for N(acetyl glycosamine);
can use this to look at problems in CNS

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Liposomes- advantages & 2 types

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-Not much immune response;
-Can control the size;
-They are self assembled;
-Stay in the body longer- more time to unload material (ex: oncolytic virus for cancer therapy)
-Some are solid like gels at room temperature and have a higher transition temperature (ex: C16--DPPC);
-Some are liquid like- unsaturated (ex: C12--DLPC)

Front 7

Synthesizing Liposomes

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DPPC + sphingolipid +cholesterol + chloroform ---> +buffer, agitate with a probe sonicator --> multilamellar vessicles--->sonic energy, unilamellar vesicles---> GPC (gel permeation chromatography separates sizes) to separate out the lipid vesicles

Front 8

DLS of Liposomes

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-Detects size differences;
-small particles have high frequency waves (more diffraction) in the Intensity vs time curve;
-large particles have low frequency waves (less diffraction) in the intensity vs time curve

Front 9

Applications of liposomes (4)

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(1) Drug delivery, example: DOX;
(2) Target drugs using hyperthermia- can tune the phase temperature of liposomes based on how saturated they are
(3) Gold nanorods + liposomes- increases temperature of liposomes
(4) cationic liposomes + DNA- ionic interaction, can be used for gene therapies. can easily get into negatively charged membranes;

Front 10

Silica nanoparticles

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-essential nutrients at low concentrations- at high concentrations it's toxic
-used for drug delivery- anticancer drug (SILYBIN)

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Silica nanoparticle synthesis

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hydrolysis and condensation of metal alkoxides;
makes Si-O-Si bond

Front 12

Magnetic nanoparticle properties

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-iron based nanoparticles
-superparamagnetic
-Fe3O4 or Fe2O3
-stabilizing matrix structure

Front 13

Magnetic nanoparticle synthesis

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Coprecipitation:
Fe(OH)2 ----(partial oxidation, HNO3)---> Fe3O4 + Fe2O3

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Magnetic nanoparticle applications (2)

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(1) Contrast agent- MRI imaging; can look at macrophage activity; can identify tumor in the liver- tumor has dark spots
(2) Hyperthermia- subject magnetic np to alternating magnetic field causes an increase in nanoparticle temperature of 2-3 degrees C. Used to treat cancer by putting nps in tumors

Front 15

Carbon nanotubes

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Single carbon tubes, have large surface area. can add drugs and couple layer by layer assembly for efficient drug delivery

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Carbon nanotube synthesis: Physical Vapor Deposition

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-3000-4000 degrees C
-laser source or arc discharging method
-Carbon vaporizes then condenses
-in presense of catalyst Fe/Co/Ni
-makes carbon nanotubes
Cons: high temp, if catalyst gets into nanotube it's toxic, impurities: fullerenes, amorphous carbon, hollow carbon balls

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Carbon nanotube synthesis: Chemical Vapor Deposition

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-1200 degrees C
-CH4 (g) + H2O2(g) ----(600-1200degreesC)---> C (s) + H2 (g)
-catalyst: ferrocene
-uniform distributed size of nanotubes

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Carbon nanotube characterization techniques (3)

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(1) Microscopy- a.) SEM/TEM can tell you size, diameter, multiwalls; b) Optical microscope; c.) AFM
(2) Spectroscopy- UV/Vis - can get concentration and look at Carbon-Carbon bonds
(3)TGA- can check for impurities- a gain in mass means metal impuraties

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Carbon nanotube biomedical applications (2)

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(1) functionalize surface with proteins, peptides, or genes
(2) filling Carbon nanotube with drug; drug delivery can be passive (nanoneedles) or active (clathrin dependent endocytosis)

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Functionalizing nanotube surface with drug examples (3)

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(1) Amphotericin B (for fungal infections)- by itself it's toxic, low solubility, aggregates. With nanotube it's less toxic and potency is preserved (covalent)
(2) Methotrexate +MWCT (covalent) ---> Jurkat cells (in vitro) showed great cellular uptake
(3) Noncovalent pi stacking of DOX

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Filling carbon nanotubes

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example- cisplatin drug
-5-27 Angstrom

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Biomedical consequences of nanotubes (2)

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(1) if they're too small nanotubes +macrophages --> lymphatic system
(2) 500nm - microm- large nanotubes + microphages --> carcinogenic, mutagenesis

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Bone properties

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-mechanical strength
-houses biochemical moieties- marrow
-metabolic functions- Ca & Phosphorous
-organic (collagen) and inorganic (hydroxy apetate) material
-1.4 million people/yr suffer from bone problems

Front 24

Implant materials (4)

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(1) metals (2) Polymers (3)Ceramics (4) Combination of polymers and ceramics

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Metals used in implants

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-great mechanical properties
-generate immune response
-detachment after prolonged use
-hip implants
-stainless steel
-Cobalt--Cromium allows, Ti, Ti alloys

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Ti Anodization

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-creates TiO2 self-aligned nanotube structure
-high surface energy wettability
-osteoblasts adhesion increased tremendously

Front 27

Ceramics for implants

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-More biocompatible compared to metals
-metal oxides- Alumina, Zirconia, Titania
-Ca3(PO4)2, TCP, hydroxyapetate
-Problem: Brittle
-nanophasic alumina: increases adhesion, better protein absorption

Front 28

Polymers for implants

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-PLA, PLGA, PGA
-biocompatible
-degradable
-synthesized in vitro
-easily processed
-long shelf life

Front 29

Lab on chip- advantages

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-Study more with less
-things in cells happen in paralell
-saves money
-use lithography to make microfluidic channels
-laminar flow through the channels- they don't mix

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Microfluidics

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The study of systems that manipulate or process small amount of fluids within geometries of 10-100 micrometers

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Intestine on a chip

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-Still being developed
-use to screen drugs in vitro because diffusing into the blood stream through the epithelial cell lining is the rate limiting step
-can test multiple drugs on tumor cells on one chip

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Two types of epithelial cells

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-90%: enterocytes with microvilli
-10%: Goblet cells (mucus)

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Liver on a chip

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-side effect of many drugs: liver toxicity
-if you maintain healthy liver state in bioreactors, they can be used to screen drugs
-A bioreactor could consist of a feeding pump, reactor tank, agitator, sensors for data aquisition, thermal jacket to keep constant temperature

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Nanomechanics

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-a branch of nanoscience that deals with mechanical properties of a physical system at nanonewton scale
-mechanics presented to cells are important- especially stem cells being used for therapies

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Engler's study of the effects of pressure on stem cells

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Applying different pressures to mesenchymal stem cells causes them to differentiate into different types of cells.
0.1 - 1kPa --> Neurons
8 - 17 kPa --> Myoblasts
25 - 40 kPa --> Osteoblasts

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Mechanical testing system

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- Measures Young's modulus - stress vs strain
- Macroscope technique - crush or stretch material

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Rheometer

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-deformation of matter under the influence of sheer stress/ rotational stress
-matter can be fluid- blood/tendon/nanofiber/nanotubes
-gives you viscosity vs strain/time/ or temp
-can use for nanomaterial optimization

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AFM

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-Can give you a force displacement curve, can convert it into force-indentation data
-use Hertz cone model equation

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Stem cells

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-enormous regenerative potential
-repair - wound healing
-controlled by mechanics (Engler study) --> causes reorganization of cytoskeleton which effects chromosomes--> protein expression
-controlled by biochemical molecules

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Stem cells + quantum dots

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Can see what stem cells differentiate into when quantum dots are inside them

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Stem cells + magnetic nps (Fe3O4)

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-Coat Fe3CO4 with dextran ---> MSC cells---> rats + mag field-->goes to site of injury

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Stem cells + gold nps

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Hyperthermia Au particle- removing artherosclerotic plaque in arteries

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Cartilage regeneration

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Cationic lyposomes with TGF-beta1 gene into mesenchymal stem cells ---> cartilage proteins upregulated; MMP-1 & MMP-2 downregulated