NBT Lecture 26

NANOTECHNOLOGY APPLICATIONS

MBT 413 Nano Biotechnology Lecture 26


Applications in Cancer biology

Nanocarriers for gene delivery



DNA delivery using nanoparticles has number of future applications

as it facilitates-

Increased transfection and trancription rates

Sustained transcription through slow release

Decreased biohazard risk in production and application

Decreased immune response

Protection of DNA and biosystem

Specific targeting



new techniques to inhibit target gene expression through transcriptional

regulation without any changes in the functions of other genes using

synthetic oligonucleotides such as

antisense DNA,

decoy oligonucleotide, and siRNA have been also considered as a novel

anti-tumor chemotherapy.

However, because pDNA and synthetic oligonucleotides are easily

degraded or metabolized, there is no cell selectivity, and enough transgene

expression or inhibition of target gene expression for effective therapy

could not be achieved by the administration of naked pDNA

or oligonucleotides.

Therefore, for effective therapy, it is essential to develop a novel carrier

that makes it possible to deliver such drugs to the target tissue or cells.



Polymers

Polymeric micelles prepared from cationic copolymer could be a novel

gene carrier. After preparing a pDNA complex (standard size 5,000–7,000

bp), the mean particle of the complex is about 50–200 nm. pDNA

entrapped in polymeric micelles is highly resistant to nuclease

degradation.

Dendrimers are also an attractive carrier for gene delivery because they

can interact on an electrostatic charge basis with biologically relevant

polyanions such as nucleic acids and pDNA as their surfaces are covered

with primary amino groups.

chemical or biological modification of the surface of dendrimers would

make them more effective drug or gene carriers.



Liposomes

Liposomes with cationic charge on their surface are novel carriers for

genes. Several kinds of liposomes for gene delivery have been

developed depending on passive or active targeting mechanisms.

System Liposome Target tissue

Capillary trapping Cationic liposome Lung

Asialoglycoprotein

receptor madiated

Asialofetuin-liposome

Galactose-liposome

Liver (hepatocyte)

Liver (hepatocyte)

Mannose receptor

mediated

Mannose liposome Liver (non-parenchymal

cell

Folate receptor

mediated

Folate-liposome Tumor cell





Hyperthermia by magnetic nanoparticles

Tumor cells are sensitive to temperature above 42ºC

Can be destroyed by increasing temp locally for 30min

Magnetic particles generate heat under alternating magnetic field





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NBT Lecture 26