Method to Conjugate Therapeutic Agents Directly to Tissue Surfaces
- 技術優勢
- Facile enzymatic controlled tissue engineeringSuccessful use under mild physiologicalconditionsDecrease need for invasive therapies
- 詳細技術說明
- Synthetic peptide-polymer conjugates that can be enzymatically coupled to cartilage providing a general means of drug delivery, tissue engineering and repair or bioadhesives administration in a biocompatible process.#materials #biomedical #therapeutics #drugdelivery
- *Abstract
-
NorthwesternSynthetic peptide-polymer conjugates areenzymatically coupled to cartilage under mild conditions through the formationof isopeptide bonds between the peptides and extra cellular matrix (ECM)proteins. The system provides a general means of drug delivery, tissue engineeringand repair or bioadhesives administration in a biocompatible process.
A variety of strategies have been employed to chemicallycouple natural or synthetic molecules to biological surfaces for drug delivery,tissue repair and tissue regeneration. In contrast the present technologyemploys a general methodology for tissue surface modification employingbiological enzyme mediated crosslinking reactions. Tissue transglutaminase(tTG), which catalyzes the crosslinking between lysine and glutamine residues,forming ε-(γ-glutaminyl) lysine isopeptide bonds, provides a vehicle toenzymatically couple synthetic molecules to tissue surfaces under physiologicconditions. Cartilage, which contains tTG and several ECM substrates of tTG,upon treatment with a variety of short synthetic peptides, containing lysine orglutamine residues conjugated with polymers, readily binds to the conjugatesunder the action of added tTG. Thus lysine conjugates (EO)2-FKG-NH2, (B2K);(PEG)-FKG-NH2, (B72K) and glutamine conjugates (EO)2-GQQQLG-NH2, (B2Q);(PEG)-GQQQLG-NH2, (B72Q) incubated (30 min, 37°C) with cartilage in thepresence of tTG showed incorporation on the tissue surface to depths of 8-13 μM(Figure 1, 2). ECM components fibronectin, collagen II, osteonectin and osteropontinall exhibit binding to the conjugates. No surface incorporation occurs in theabsence of tTG. The lysine and glutamine peptides employed were rationallydesigned to afford favorable tTG substrates. Peptide conjugates of hyaluronicacid (FKG-HA) and functionalized hydrocortisone (HC-GFKG) have been similarlyincorporated into cartilage surfaces.
The minimally invasive administration of tTG andsynthetic molecules to other tissue surfaces provides a novel means to delivera wide range of functional polymers, biomolecules and therapeutic agents.
Figure 1 (a) Image of cartilage treated with B72K peptide without tTG (b) Image of cartilage treated with B2K and tTG showing stained surface bound conjugate (arrows).
Figure 2 Graph comparing the thickness of cartilage surface tissue modified by four peptide conjugates
Bar = 50 μM.
- *Inventors
- Phillip Messersmith*Marsha Ritter-Jones
- *Publications
- Jones, MRand Messersmith, P (2007) Facile coupling of synthetic peptides andpeptide-polymer conjugates to cartilage via transglutaminase enzyme. Biomaterials. 28: 5215-5224.
- 國家/地區
- 美國
