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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