Nanomedicine Review By Nanotech Group Alexandria

 

Nanotechnology 

Nanotechnology is the creation of useful materials, devices, and systems through the control of matter on the nanometerlength scale. This takes place at the scale of atoms, molecules, and supramolecular structures

History Nanotechnology and nanoscience star ted in the ear ly 1980s with two major developments:

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q the bir th of Cluster Science q the invention of the Scanning Tunneling Micr oscope (STM)

IBM Fellow ‘Don Eigler’ was the first to accurately manipulate individual atoms on a surface

Atomic Force Microscope (AFM) was invented in 1986 Providing :

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q better resolution q higher contr ol

Atomic Force Microscope (AFM)

Nanotechnological approaches : vBottom up approach 

involves assembling structures atom-byatom or molecule-by-molecule

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vTop-down approach 

involve breaking down of macros, Rarely used in Nanomedicine

Nanomedicine 

Nanomedicine may be defined as the application of nanotechnolog y by cr eating devices and

Gordon, N., Sagman, U.: Nanomedicine Taxonomy. Canadian Institute of Health Research & Canadian NanoBusiness Alliance (2003).

Definition Nanodevices are much simpler polymer backbone structure (<100nm) attached to it some nanotools

Objectives

Make the device smarter and even more versatile so it can do what brute force could not

Nanomaterials

Nanomaterials 

Graphene sheets rolled into tubes or sphere

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unique mechanical and electrical proper ties

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carbon Nanotubes

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heat resistance

Nanomaterials 

Quantum-size effects are observed

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Semiconductor particles

quantum confinement

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some metal particles

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surface Plasmon resonance

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magnetic materials

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superparamagnetism

NANO-TOOLS

Nanopores are small holes in a surface that helps selecting particles to pass through depending on its size, voltage.

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At this size

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Pass: Small molecules as o2, nutrients

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Block: Large IG and graft rejecting viruses

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T his Concept would be of a g reat value in mana gement of any hor mone, Enzyme deficient disease as an encapsulated Gland cells could be used to r eplace Nor mal

Function : enhanced drug characteristics üimmune stealth ürenal clearance. example : peginterferon alpha-2a for treatment of cancer.In clinical practice once weekly dose was more effective than triweekly dose of interferon alpha-2a

Alza's Stealth liposomes encapsulate a drug (red) in a phospholipid bilayer (blue and white). A polyethylene glycol coating (green) allows the liposomes to evade the immune system, increasing the half-life of the drug in the body.

Förster Resonance Energy Transfer qConcept:

Distance-Dependent ener g y tr ansfer between two chr omophor es in w hich excitation is tr ansfer r ed fr om a donor molecule to an acceptor molecule without emission of a photon as long as the absor ption qspectr A pplication um over lap the emission spectr um it is a powerfull r epor ter for the separ ation of two chr omophor es

http://www.invitrogen.com

v Quantum Dots are Nanocrystal particles with Quantum confinement properties v they can be excited to fluorescence with different wavelengths of Electromagnetic radiation v The resulting fluorescent color can be adjusted by changing the Qdot’s size Further explanation is and composition. available at the presentation end

of the

q Structure : Thin metallic shells of a diameter ranging from a hundred to a few hundred nanometers

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Concept: their small size allows them to absorb and scatter light at different wavelengths, depending on their size and their surface plasmonic resonance

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Applications:

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Photothermal ablation

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Imaging and detection techniques

Definition

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Are large complex man-made molecule with a very welldefined chemical structure and perfectly spherical shape with a highly branched 3 dimensional architecture

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Molecular structure

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Core

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Branches

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cavities

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Terminals ends

Manufacturing

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Dendrimers Are produced in an accumulative (iterative) sequence of reactions steps, in which each additional interaction leads to a higher generation and doubling The number of active sites

Manufacturing

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Synthesis :

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Branching unit is added Dendron arms are created then added to the desired core to core simultaneously many iterative reactions Reduce iterative reactions Result in Results in imperfect samples and near-perfect dendrimer Structure side reactions

potential Br anches

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T hey conjugate various types of molecules W hich is classified into I. Antitoxic particles II. Solubility modifiers III.Active receptor targeting IV.Nanodecoys V. Imaging tags. 

Inter nal Cavities:

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Encapsulation

Back bone for nanodevices

Par ticle

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Current Dendritic products Product

Application

Company

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Vivagel

VaginalGel , using Nanodecoys to prevent HIV infection

Starpharma

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Strarus CS

Cardiac Marker

Dade Behring

SuperFect

Gene Transfection

Qiagen

Alert Ticket

Anthrax

Us Army Research Lab

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Detection

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Dendrimer s can be ver y useful in cr eating a multipur pose NanoDevice, as it can

Cancer management

Demonstration of Nanomedicine on cancer management v Smar t dr ugs v Tar geted Nanopar ticles v Tr ojan hor ses v Nanoshells Assisted Photo-ther mal T her apy

v Imaging: 

-Dendrimer s-based MRI contr ast a gents 

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v Lab : 

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-Qdots imaging

-cantilever s

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Smart drugs :

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drugs that are only medically active in specific circumstances, as Enzymeactivated drugs

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Targeted Nanoparticles:

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Targeting are either

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Passive : nanodimensionly mediated via EPR Active : Receptormediated cell-specific targeting

Aurimune drug by Cytimmune

Trojan horse:

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Polymeric liposome analogue with a drug payload inside a hydrophobic core

gate may be peptide anti-body or proteins which may elicitnucleic an immune Excellent vector for delivering acids in Elegant example for multifunctional nano mer back bone with hydrophobic side nse cells device

Nanoshells are tuned to absorb specific wavelengths depending on: -size - core to shell diameter ratio Nanoshell

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generate heat

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NIR

800-1200nm

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cell death

Suppresses the immune reaction

enhance biocompatibility

HER2 over expressed on ~ 30% of breast cancer cells

Nanoshells are attached to tumor cells by active targeting

vImaging 

Dendrimer-based MRI contrast agents

Concept :

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Gadolinium groups (Magnevist®) were attached to PAMAM Dendrimers surface terminal groups

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Quantum Dots and Imaging

Qds can be used for the study of live cell single molecule dynamics , monitoring of intr acellular pr otein –pr otein inter actions , disease detection in deeper tissues , detection of cancer tumor cells based on selective binding of bioconjugated QDs

Quantum Dots and Imaging

The figure above shows green Qdots conjugated to streptavidin , the image shows F-actins of fixed fibroblasts.

This shows human living cancer cells incubated with red fluorescent CdSe ZnS Qdots conjugated to TAT peptides, their intracellular aggregation pattern suggests their presence inside intracellular vesicles

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Cantilever Cantilevers are semiconductor beams formed by Nanolithographic techniques that can be used to detect various molecules or proteins in the bloodstream providing a non-invasive rapid screening and detecion tool

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Cantilever

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Reference: cancer.gov>>Arun Majumdar, University of California at Berkeley

Cantilever

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Reference: cancer.gov>>Arun Majumdar, University of California at Berkeley

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It’s the study of pathological and toxicological effects that are unique to the size of the nanomaterials ,which are not observed on bulk materials, their toxicity is a Multi disciplinary area concerning effects related to their small size, larger surface area , nature, solubility, agglutination, higher chemical and biological activity .

Toxicity of Nanoparticles v Nanometals v Nanoshells v Nanotubes v Fullerenes v 

Toxicity of Nanoparticles v Nanometals v v v v v v v v v Nanoshells v

Toxicity of Nanoparticles v Nanometals v Nanoshells 

Regarding gold nothing has yet been established on health hazards caused by its nano particles used in Nanoshells’ manufacturing , and a study on zebra fish treated with silver and gold resulted that gold was completely inert with no pathognomonic effects at all size and levels on the contrary to silver

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v Nanotubes v Fullerenes

Toxicity of Nanoparticles v Nanometals v Nanoshells v Nanotubes 

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- produce a tissue reaction similar to asbestos - thin pins like shape penetrate the lining endothelium of the lung produces proinflammatory effects - DNA damage at low levels on human lung endothelial cells

v Fullerenes 

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Toxicity of Nanoparticles v Nanometals v Nanoshells v Nanotubes v Fullerenes 

their toxic effect results from tetrahydrofuran used in preparing the 30 nm–100 nm particles of C60 , as so removing The TetraHydroFuran from the C60 particle results in a marked decrease of its toxicity

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Questions ?

Thank You

Nanotech students group §Ali Al –Nowaem §Karim Ismail §Hesham Ghoneim §Momen Zalabany §Passent Maged

Excitation of Qdots

Qdots in details.

Mechanism

and increase the Band gap

Bohr Radius explanation

Emission mechanism 1

Emission mechanism 2