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Transcript
Self-assembly in Nature
Nano
Self-assembly of amphiphilic molecules
spherical micelles
cylindrical
micelles
nanotubes
vesicles (liposomes)
Drug delivery systems
1. Direct conjugation of drugs or therapeutic proteins
to macromolecules such as polymers and proteins.
2. Encapsulation of hydrophobic drugs at the inside of the micelles or dendrimers
3. Entrapment of water-soluble drugs at the inside cavity of vesicles
The enhanced permeability and retention (EPR) effect
Macromolecules cannot pass through the capillary walls of normal tissue. The
entry of macromolecules into tumor tissue takes place in the capillaries
where blood flow is diminished and nutrients transfer into the tissue. In
contrast to the blood capillaries in most normal tissues, the endothelial layer
of the capillaries in the tumor tissue is fenestrated and leaky so that
macromolecules and other nanoparticles reach the malignant tissue. Tumor
tissue generally has a defective lymphatic drainage system with the result
that macromolecules are retained and can subsequently accumulate in solid
tumors.
pH-Responsive Nanocapsules
DLS
18nm
pH 7
HCl
3nm
pH 5
1
10
100
Radius (nm)
Release of Calcein
100
Release / %
pH 5
pH 7
80
60
40
pH drop
20
pH drop to 5
0
0
50
100
150
Time (h)
J. Am. Chem. Soc. 2004, 126, 12724
200
Vesicle
d = 36 nm
Micelle
d = 6 nm
암세포에만 약물을 방출하는 나노 운반체
Carbohydrate – Protein Multivalent Interactions
antigen
carbohydrate
Antigen
Kiessling et. al. J. Am. Chem. Soc. 2002, 124, 14922.
Mannose-Coated Supramolecules
1800
OH
OH
OH
lectin protein
OH
O
O
O
12
glycocluster
Relative activity per mannose
HO
d= 40 nm
HO
1600
OH
HO
OH
HO
HO
OH
OH
O
HO
O
O
O
O
HO
OH
O
O
O
O
O
O
O
O
1000
O
23
800
O
O
600
400
200
n.d.
0
Vesicle
d= 20 nm
Sphere
Galactose
Micelle
Cylinder
d= 10 nm
O
Hemagglutination Inhibition Assay
1
nm 16333
J. Am. Chem. Soc. 2005,50127,
Chem. Commun. 2005, 2035
J. Am. Chem. Soc. 2007, in press
OH
OH
1400
1200
HO
OH
OH
HO
HO
2
3
100 nm
100 nm
O
OH
Selective Binding of Supramolecules to Bacterial Cells
E. coli
E. coli
pili
Binding to
E. coli ORN 178
TEM
100 nm
E. Coli (ORN 178) + spheres
100 nm
E. Coli (ORN 178) + cylinders
100 nm
E. Coli (ORN 208)
Binding of Bacterial Cells
Selective-binding
+
Pathogen
ß-sheet assembly
=
=
HO
HO O
HO
HO
O
D-mannose-binding protein
Pathogen