RESEARCH PAPER Polyvalent integrin antagonist-decorated superparamagnetic iron oxide nanoparticles for triggering apoptosis in human leukemia cancer cells Rıdvan Say • Suzan Yazar • Alper Ug ˘ur • Deniz Hu ¨r • Adil Denizli • Arzu Erso ¨z Received: 9 December 2011 / Accepted: 30 November 2012 / Published online: 14 December 2012 Ó Springer Science+Business Media Dordrecht 2012 Abstract Integrin family members are the main mediators of cell adhesion to the extracellular matrix and active as intra- and extracellular signaling mole- cules in a variety of processes. They bind to their ligands by interacting with short amino acid sequences, that is, RGD (arginine-glycine-aspartic acid) sequence. RGD sequences have been used to enhance cell binding to artificial surfaces, so RGD mimics have been used to block integrin binding to its ligand. Integrin–ligand interactions are dependent on divalent cations, and Mg 2? provide higher-affinity binding to ligand for many integrins. In this study, we have designed new integrin antagonists using methacryloyl amidoaspartic acid (MAASP) monomer-conjugated silanized super para- magnetic iron oxide nanoparticles (SPIONs, the size of the nanoparticles was verified with an average size of 32.6 nm) and poly(MAASP-co-EDMA) shell-deco- rated silanized SPIONs. Several mechanisms have been proposed to describe uptake of modified SPIONs into the cells, including receptor-mediated endocytosis. Our aim is to bind these modified SPIONs to the integrin- mediated aspartic acid ends of MAASP monomers and block integrin binding to their ligand. Keywords MAASP monomers Á RGD mimic Á Poly(MAASP-co-EDMA) shell Á Super paramagnetic iron oxide nanoparticles (SPIONs) Introduction The adhesive interactions between a cell and its surrounding extracellular matrix regulate its morphol- ogy, migratory properties, growth, and differentiation. The major components in cell–matrix adhesions are integrins, a large family of trans membrane heterodi- mers made up of alpha and beta subunits that are non- covalently associated (Burridge and Chrzanowska- Wodnicka 1996; Shakibaei et al. 2008). Integrins are expressed by all multicellular animals; in mammals, 19 a and 8 b subunit genes encode polypeptides that combine to form 25 different receptors (Humphries 2000). Integrin family members are plasma membrane receptors and are active as intra- and extracellular signaling molecules in a variety of processes including embryogenesis, hemostasis, angiogenesis, immune R. Say (&) Á A. Ug ˘ur Á D. Hu ¨r Á A. Erso ¨z Kimya Bo ¨lu ¨mu ¨, Fen Faku ¨ltesi, Anadolu Universitesi, Yunus Emre Kampu ¨su ¨, 26470 Eskisehir, Turkey e-mail: rsay@anadolu.edu.tr S. Yazar Sanovel Pharmaceutical Company, Istanbul, Turkey D. Hu ¨r Plant, Drug and Scientific Research Center, Anadolu University, Eskisehir, Turkey A. Denizli Department of Chemistry, Hacettepe University, Ankara, Turkey 123 J Nanopart Res (2013) 15:1350 DOI 10.1007/s11051-012-1350-2