SMARTSTRUCTURES

Synthesis of Smart Virus-like Hierarchical Structures Based-on Polymer-Peptide Conjugates and the Potential Application in Drug Delivery

Coordinatore	UNIVERSITY OF BRISTOL    more  Organization address address: TYNDALL AVENUE SENATE HOUSE city: BRISTOL postcode: BS8 1TH contact info Titolo: Ms. Nome: Audrey Cognome: Michael Email: send email Telefono: +44 117 3317371
Nazionalità Coordinatore	United Kingdom [UK]
Totale costo	209˙033 €
EC contributo	209˙033 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2011-IEF
Funding Scheme	MC-IEF
Anno di inizio	2012
Periodo (anno-mese-giorno)	2012-07-01   -   2014-06-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	UNIVERSITY OF BRISTOL  Organization address address: TYNDALL AVENUE SENATE HOUSE city: BRISTOL postcode: BS8 1TH contact info Titolo: Ms. Nome: Audrey Cognome: Michael Email: send email Telefono: +44 117 3317371	UK (BRISTOL)	coordinator	209˙033.40

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 Obiettivo del progetto (Objective)

'In this proposal, we intend to combine the advantages of virus and polymersome structural motifs into one integrated model as a promising strategy to construct hybrid structures that are efficient delivery vehicles. First, folic acid-modified polyN-(2-hydroxypropyl)methacrylamide-poly(L-cysteine) conjugate (FA-PHPMA-b-PLC) will be synthesized. The biocompatible PHPMA is used as the hydrophilic part, and PLC is chosen for its ability to aggregate in water (by either hydrogen or covalent bonding via beta-sheet formation or disulphide linkage). Not only do the thiol groups in PLC chain play an important role for covalent loading of drugs/proteins/genes via thiol exchange with disulfide groups, but also the oxidation of the cysteine residues to form intra- and intermolecular disulfide bridges further stabilize the polymersome structure. After forming the polymersome, the biomolecules will be incorporated by either covalent or noncovalent mechanisms. Finally, zinc oxide nanoparticles modified by disulfide-linked pyridine will be covalently encapsulated into the PLC shell to obtain the hybrid virus-like structure with ZnO nanoparticles as a key component of the coronal layer. We anticipate that the constructed hybrid structure will enter the target cell by endocytosis. The low pH in the endosome (pH~5) will then accelerate the dissolution of the ZnO nanoparticles and release the biomolecules. Subsequently, glutathione in the cytoplasm will reduce the cross-linked disulfides in PLC shell and lead to the disassembly of the polymersome. Therefore, as a new hybrid structure that integrates significant advantages of both the polymersome and virus models of biomolecule delivery, it is reasonable to believe that it will provide a new advance for the design of delivery vehicles for the cure of cancer-related diseases.'