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Polyvalent integrin antagonist-decorated superparamagnetic iron oxide nanoparticles for triggering apoptosis in human leukemia cancer cells

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Abstract

Integrin family members are the main mediators of cell adhesion to the extracellular matrix and active as intra- and extracellular signaling molecules 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 Mg2+ 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 paramagnetic 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-decorated 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.

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References

  • Akers WJ, Zhang Z, Berezin M, Ye Y, Agee A, Guo K et al (2010) Targeting of ανβ3-integrins expressed on tumor tissue and neovasculature using fluorescent small molecules and nanoparticles. Nanomedicine 5:715–726

    Article  CAS  Google Scholar 

  • Assa-Munt N, Jia X, Laakkonen P, Ruoslahti E (2001) Solution structures and integrin binding activities of an RGD peptide with two Isomers. Biochemistry 40:2373–2378

    Article  CAS  Google Scholar 

  • Beer AJ, Schwaiger M (2008) Imaging of integrin αvβ3 expression. Cancer Metastasis Rev 27:631–644

    Article  CAS  Google Scholar 

  • Brooks PC, Clark RAF, Cheresh DA (1994) Requirement of vascular integrin αvh3 for angiogenesis. Science 264:569–571

    Article  CAS  Google Scholar 

  • Burridge K, Chrzanowska-Wodnicka M (1996) Focal adhesions, contractility, and signaling. Annu Rev Cell Dev Biol 12:463–519

    Article  CAS  Google Scholar 

  • Carlson CB, Mowery P, Owen RM, Dykhuizen EC, Kiessling LL (2007) Selective tumor cell targeting using low-affinity, multivalent interactions. ACS Chem Biol 2:119–127

    Article  CAS  Google Scholar 

  • Cheresh DA, Spiro RC (1987) Biosynthetic and functional properties of an Arg-Gly-Asp-directed Receptor Involved in human melanoma cell attachment to vitronectin, fibrinogen, and von Willebrand Factor. J Bio Chem 262:17103–17711

    Google Scholar 

  • Dransfield I, Cabanas C, Craig A, Hogg N (1992) Divalent cation regulation of the function of the leukocyte integrin LFA1. J Cell Biol 116:219–226

    Article  CAS  Google Scholar 

  • Emsley J, Knight CG, Farndale R, Barnes M, Liddington R (2000) Structural basis of collagen recognition by integrin α2β1. Cell 101:47–56

    Article  CAS  Google Scholar 

  • Gupta AK, Gupta M (2005) Synthesis and surface engineering of superparamagnetic iron oxide nanoparticles for biomedical applications. Biomaterials 26:3995–4021

    Article  CAS  Google Scholar 

  • Hood JD, Cheresh DA (2002) Role of integrins in cell invasion and migration. Nat Rev Cancer 2:91–100

    Article  Google Scholar 

  • Humphries MJ (2000) Integrin structure. Biochem Soc Transac 28:311-340

    Google Scholar 

  • Hür D, Ekti SF, Say R (2007) N-Acylbenzotriazole mediated synthesis of some methacrylamido amino acids. Lett Org Chem 4:585–587

    Article  Google Scholar 

  • Keçi1i R, Atılır Özcan A, Ersöz A, Hür D, Denizli A, Say R (2011) Superparamagnetic nanotraps containing MIP based mimic lipase for biotransformations uses. J Nanoparticle Res 13:2073–2079

    Google Scholar 

  • Knight CG, Morton LF, Peachey AR, Tuckwell DS, Farndale RW, Barnes MJ (2000) The collagen-binding A-domains of integrins α1β1 and α2β1 recognize the same specific amino acid sequence, GFOGER, in native (Triple-helical) collagens. J Biol Chem 275:35–40

    Article  CAS  Google Scholar 

  • Kobayashi H, Lin PC (2006) Nanotechnology for antiangiogenic cancer therapy. Nanomedicine 1:17–22

    Article  CAS  Google Scholar 

  • Kok JR, Schra AJ, Bos EJ, Moorlag HE, Asgeirdorrir SA, Everts M et al (2002) Preparation and fictional evaluation of RGD-modified proteins as αvβ3 integrin directed therapeutics. Bioconjugat Chem 13:128–135

    Article  CAS  Google Scholar 

  • Lee H, Yu MK, Park S, Moon S, Min JJ, Jeong YY et al (2007) Thermally cross-linked superparamagnetic iron oxide nanoparticles: synthesis and application as a dual imaging probe for cancer in vivo. J Am Chem Soc 129:12739–12745

    Article  CAS  Google Scholar 

  • Leitinger B, McDowall A, Stanley P, Hogg N (2000) The regulation of integrin function by Ca2+. Biochim Biophys Acta 1498:91–98

    Article  CAS  Google Scholar 

  • Nakamura H, Ito N, Kotake F, Mizokami Y, Matsuoka T (2000) Tumor-detecting capacity and clinical usefulness of SPIO-MRI in patients with hepatocellular carcinoma. J Gastroenterol 35:849–855

    Article  CAS  Google Scholar 

  • Perez JM, Simeone FJ, Saeki Y, Josephson L, Weissleder R (2003) Viral-induced self-assembly of magnetic nanoparticles allows the detection of viral particles in biological media. J Am Chem Soc 125:10192–10193

    Article  CAS  Google Scholar 

  • Pierschbacher MD, Ruoslahti E (1984) Cell attachment activity of fibronectin can be duplicated by small synthetic fragments of the molecule. Nature 309:30–33

    Article  CAS  Google Scholar 

  • Ruoslahti E (1996) RGD and other recognition sequences for integrins. Annu Rev Cell Dev Biol 12:697–715

    Article  CAS  Google Scholar 

  • Ruoslahti E, Pierschbacher MD (1987) New perspectives in cell adhesion: RGD and integrins. Science 238:491–497

    Article  CAS  Google Scholar 

  • Schwertmann U, Cornell RM (1991) Superparamagnetic iron oxides in the laboratory: preparation and characterization. VCH, Weinheim

    Google Scholar 

  • Shaker A (2003) Mousa, αv vitronectin receptors in vascular-mediated disorders. Med Res Rev 23:190–199

    Article  Google Scholar 

  • Shakibaei M, Csaki C, Mobasheri A (2008) Diverse roles of integrin receptors in articular cartilage. Adv Anat Embryol Cell Biol 197:1–60

    Article  CAS  Google Scholar 

  • Stupack DG (2007) The biology of integrins. Oncology 21:6–12

    Google Scholar 

  • Sunderland CJ, Steiert M, Talmadge JE, Derfus AM, Barry SE (2006) Targeted nanoparticles for detecting and treating cancer. Drug Dev Res 67:70–93

    Article  CAS  Google Scholar 

  • Tagalakis AD, Grosse SM, Meng QH, Mustapa MFM, Kwok A, Salehi SE et al (2011) Integrin-targeted nanocomplexes for tumor specific delivery and therapy by systemic administration. Biomaterials 32:1370–1376

    Article  CAS  Google Scholar 

  • Villard V, Kalyuzhniy O, Riccio O, Potekhin S, Melnik TN, Kajava AV et al (2006) Synthetic RGD-containing α-helical coiled coil peptides promote integrin-dependent cell adhesion. J Peptide Sci 12:206–212

    Article  CAS  Google Scholar 

  • Williams CH, Kajander T, Hyypiä T, Jackson T, Sheppard D, Stanway G (2004) Integrin αvβ6 is an RGD-dependent receptor for coxsackievirus A9. J Virol 6967–6973

  • Wong NC, Mueller BM, Barbas CF, Ruminski P, Quaranta V, Lin ECK et al (1998) αv integrins mediate adhesion and migration of breast carcinoma cell lines. Clin Exp Metastasis 16:50–61

    Article  CAS  Google Scholar 

  • Xavier M, Karin MA, Fred R, Ralph W, Lee J (2006) Nanoparticle imaging of integrins on tumor cells. Neoplasia 8:214–222

    Article  Google Scholar 

  • Yang H, Zhuang Y, Sun Y, Dai A, Shi X, Wu D et al (2011a) Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles. Biomaterials 32:4584–4593

    Article  CAS  Google Scholar 

  • Yang X, Hong H, Grailer JJ, Rowland IJ, Javadi A, Hurley SA et al (2011b) cRGD-functionalized, DOX-conjugated, and 64Cu-labeled superparamagnetic iron oxide nanoparticles for targeted anticancer drug delivery and PET/MR imaging. Biomaterials 32:4151–4160

    Article  CAS  Google Scholar 

  • Zhang C, Jugold M, Woenne EC, Lammers T, Morgenstern B, Mueller MM et al (2007) Specific targeting of tumor angiogenesis by RGD-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 1.5-T magnetic resonance scanner. Cancer Res 67:1555–1562

    Article  CAS  Google Scholar 

  • Zhang S, Zou L, Zhang D, Pang X, Yang H, Xu Y (2011) GoldMag nanoparticles with core/shell structure: characterization and application in MR molecular imaging. J Nanopart Res 1–10

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Authors and Affiliations

  1. Kimya Bölümü, Fen Fakültesi, Anadolu Universitesi, Yunus Emre Kampüsü, 26470, Eskisehir, Turkey

    Rıdvan Say, Alper Uğur, Deniz Hür & Arzu Ersöz

  2. Sanovel Pharmaceutical Company, Istanbul, Turkey

    Suzan Yazar

  3. Plant, Drug and Scientific Research Center, Anadolu University, Eskisehir, Turkey

    Deniz Hür

  4. Department of Chemistry, Hacettepe University, Ankara, Turkey

    Adil Denizli

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  1. Rıdvan Say
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  2. Suzan Yazar
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  3. Alper Uğur
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  4. Deniz Hür
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  5. Adil Denizli
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  6. Arzu Ersöz
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Correspondence to Rıdvan Say.

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Say, R., Yazar, S., Uğur, A. et al. Polyvalent integrin antagonist-decorated superparamagnetic iron oxide nanoparticles for triggering apoptosis in human leukemia cancer cells. J Nanopart Res 15, 1350 (2013). https://doi.org/10.1007/s11051-012-1350-2

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  • DOI: https://doi.org/10.1007/s11051-012-1350-2

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