Impact Factor 6.378

Literature Meet-ing M. Ehsan

Bionano Chemistry Lab

Introduction

Supramolecular Polymer A supramolecular polymer is a polymer whose monomer repeat units are held together by noncovalent bonds.

Coordination π-π interactions hydrogen bonding

Quadruple hydrogen bonds

Hydrogen Bond Quadruple AngewChemIntEd 1998 v37 p75

EurJOrgChem page2565 year1998

• Peptide-amphiphiles are attractive candidate biomaterials for

bio-nanotechnology and tissue engineering

• applications ranging from controlled gene and drug release,

• skin care,

• nanofabrication,

• biomineralization,

• membrane protein stabilization

• 3D cell culture and tissue engineering.

Synthetic Strategy

Fig. 1 Schematic representation of the chemical structures of pyrenei midazolium labeled peptide and viologen function-alised PNIPAAm and the formation of a ternary complex with CB[8].

Cucurbiturils are macrocyclic molecules made of glycoluril (=C4H2N4O2) monomers linked by methylene bridges.

drug delivery, asymmetric synthesis, molecular switching, and dye tuning

Cucurbit[8]uril (CB[8]) ternary complex system offers strong binding of two complementary motifs (binding constants Keq = 1012 M-2) in water

The CB[8] is an attractive choice for building stable, modular supramolecular structures in an aqueous environment via a non-covalent route.

Acta Crystallogr B, 1984, 382-387

Cucurbituril gyroscope AngewChem-IntEd 2002 v41 p275

Supramolecular Polymeric Peptide Vesicle Formation

Fig. 2 Schematic representation of the temperature induced formation of a supramolecular

polymeric peptide vesicle.

Thermoresponsive Behaviour

Fig. Thermoresponsive behaviour of 1 + 2 with and without CB[8] (0.05 mM).

TEM micrographs of supramolecular vesicles at 37 oC (solution concentration = 0.05 mM).

Particle size distributions of supramolecular vesicles at 37 oC.

Critical Aggregation Concentration (CAC)

Figure : Determination of the CAC of the supramolecular vesicles in (a) deionised water and (b) 1X phosphate buffer saline (PBS) solution containing 1% fetal bovine serum (FBS) at pH 7.4

Basic fibroblast growth factor (bFGF)

Basic fibroblast growth factor is a mitogenic cytokine protein

Regulates many aspects of cellular activity, such as cell migration and ex-tracellular matrix metabolism.

bFGF degrades rapidly when the external environment is above 40 oC or when the pH is less than 5,

Heparin is required to stabilise the protein and to

preserve its bioactivity The efficacy of bFGF in vivo is also limited

its short lifetime and

susceptibility to enzymatic degradation

http://en.wikipedia.org/wiki/Basic_fibroblast_growth_factor

• Various approaches have been proposed for the stabilization of bFGF. • These include the Chemical modification techniques, Encapsulation in gels and Powder formulation.

• Vesicles are highly attractive carriers for proteins due to their hydrophilic

interior.• minimises the risk of protein denaturation as it does not expose

the protein to extremes in temperatures or organic solvents

Encapsulation Effect on the Immunoreactivity of bFGF

Fig. 4 (a) Assessment of immunoreactive bFGF in vesicles after encapsulationat various times

Bioactivity of bFGF

(b) Bioactivity of bFGF following storage in vesiclesafter encapsulation at various times.

Effect of freeze-thaw denaturing conditions as compared to heparin treatment on the bioactivity of bFGF encapsulated in the vesicles.

Release Behavior

Figure : bFGF release (37 oC) from the vesicles made from the ternary complexes.

Conclusion

• Protein-friendly nature of the vesicles was demonstrated

by encapsulating bioactive bFGF into the supramolecular nanocarriers without the use of stabilising agents

• The supramolecular vesicles could potentially be used as in-jectable carriers for the release of bioactive cytokines for tis-sue repair and other related applications