Protein imprinted nanoparticles (PINAPLES) as artificial antibodies

Samenvatting

We propose here a unique, innovative and versatile concept to make polymer nanoparticles having imprints of membrane proteins on their surface. Such an imprint is a shape complementary to the protein template, having functional groups positioned such that they interact with the template. It would allow selective and reversible binding of the protein of interest and would open up a wide range of applications such as protein recognition for analytical purposes, separation of proteins, or binding of particles to cells or tissues for diagnostic or drug targeting purposes.
Membrane proteins are particularly interesting because they serve many biological functions and are often the therapeutic targets to treat a variety of diseases.
We will focus on the preparation of degradable particles which will bind to membrane proteins in specific cells, tissues, or microorganisms, aiming at a new generation of drug carriers which display unprecedented intrinsic targeting properties. Besides, the particles may act as a drug themselves, since they may be capable of blocking imprinted membrane receptors or inhibit proliferation of bacteria or viruses, thereby bringing about a new area of research called polymer drugs. Finally, the particles can be a favorable substitute for monoclonal antibodies in a variety of applications, having the advantages of being cheaper, more stable, non-immunogenic, and re-usable.

Output

Proefschrift

  • J.P. Schillemans(2010): Charged hydrogels for post-loading, release, and molecular imprinting of proteins  29 november 2010
  • E. Verheyen(2011): From imprinting efforts to new concepts in controlled release of proteins , Utrecht  9 november 2011

Wetenschappelijk artikel

  • C.F. van Nostrum(2005): Molecular imprinting: a new tool for drug innovation Drug Discovery Today: Technologies pp. 119 - 124
  • C.F. van Nostrum, B. Lucas, S.C. De Smedt, F.M. Flesch, J. Demeester, T.G. van Thienen(2005): On the synthesis and characterization of biodegradable dextran nanogels with tunable degradation properties Macromolecules pp. 8503 - 8511
  • J.P. Schillemans, C.F. van Nostrum(2006): Molecularly imprinted polymer particles: synthetic receptors for future medicine Nanomedicine pp. 437 - 447
  • F.M. Flesch, W.E. Hennink, J.P. Schillemans, C.F. van Nostrum(2006): Synthesis of bilayer-coated nanogels by selective crosslinking of monomers inside liposomes Macromolecules pp. 5885 - 5890
  • C.F. van Nostrum, J.P. Schillemans, W.E. Hennink(2010): The effect of network charge on the immobilization and release of proteins from chemically crosslinked dextran hydrogels European Journal of Pharmaceutics and Biopharmaceutics pp. 329 - 335
  • E. Verheyen, L. Delain-Bioton, S. van der Wal, N. el Morabit, A. Barendregt, W.E. Hennink, C.F. van Nostrum(2010): Conjugation of methacrylamide groups to a model protein via a reducible linker for immobilization and subsequent triggered release from hydrogels Macromolecular Bioscience pp. 1517 - 1526
  • E. Verheyen, S. van der Wal, H. Deschout, K. Braeckmans, S. de Smedt, A. Barendregt, W.E. Hennink, C.F. van Nostrum(2011): Protein macromonomers containing reduction-sensitive linkers for covalent immobilization and glutathione triggered release from dextran hydrogels Journal of Controlled Release pp. 329 - 336
  • E. Verheyen, J.P. Schillemans, M. van Wijk, M.A. Demeniex, W.E. Hennink, C.F. van Nostrum(2011): Challenges for the effective molecular imprinting of proteins Biomaterials pp. 3008 - 3020
  • J.P. Schillemans, E. Verheyen, A. Barendregt, W.E. Hennink, C.F. van Nostrum(2011): Anionic and cationic dextran hydrogels for post-loading and release of proteins Journal of Controlled Release pp. 266 - 271

Professionele publicatie

  • C.F. van Nostrum: antilichamen van kunststof

Kenmerken

Projectnummer

700.53.422

Hoofdaanvrager

Dr. C.F. van Nostrum

Verbonden aan

Universiteit Utrecht, Faculteit Bètawetenschappen, Departement Farmaceutische Wetenschappen

Uitvoerders

Dr. L. Delain-Bioton, Dr. F.M. Flesch, Ir. A.P.C.A. Janssen, Ing. N. El Morabit, Drs. J.P. Schillemans, Dr. E. Verheyen

Looptijd

01/07/2004 tot 18/03/2011