Synthesis and characterization of PAMAM dendrimer-based multifunctional nanodevices for targeting αvβ3 integrins

Wojciech G. Lesniak, Muhammed S.T. Kariapper, Bindu M. Nair, Wei Tan, Alan Hutson, Lajos P. Balogh, Mohamed K. Khan

Research output: Contribution to journalArticlepeer-review


We have synthesized a stable and clinically relevant nanodevice (cRGD-BT-ND; ND for short) that exhibits superior binding to the biologic target αvβ3 integrins, when either compared to the same free cRGD peptide or to the biotinylated nanodevice without covalently attached peptides (BT-ND). Selective targeting of αvβ 3 integrins was achieved by coupling cyclic cRGD peptides to the nanodevice (ND) surface, while biotin groups (BT) were used for amplified detection of bound cRGD-BT-ND by anti-biotin antibody or avidin linked to horseradish peroxidase after binding. The synthesis involved the following steps: the amino-terminated ethylenediamine core generation 5 poly(amidoamine) (PAMAM_E5.NH2) dendrimer was first partially acetylated and then biotinylated, and residual primary amine termini were converted to succinamic acid groups (SAH), some of which finally were conjugated with cRGD peptide residues through the amino group of the lysine side chain. The starting material and all derivatives were extensively characterized by polyacrylamide gel electrophoresis (PAGE), size exclusion chromatography (SEC), potentiometric acid-base titration, MALDI-TOF, and NMR. Cytotoxicity of all dendrimer derivatives was examined in B16F10 melanoma cell cultures using the XTT colorimetric assay for cellular viability. Binding of nanodevices to the biological target was determined using plates coated with human αvβ3 integrin and αvβ 3 receptor expressing human dermal microvascular endothelial cells (HDMECs). The PAMAM_E5.(NHAc)72(NHBT)8(NHSAH) 35(NHSA-cR GD)4 nanodevice is nontoxic within physiologic concentration ranges and specifically binds to the αvβ 3 integrins, apparently much stronger than the cyclic cRGD peptide itself.

Original languageEnglish (US)
Pages (from-to)1148-1154
Number of pages7
JournalBioconjugate Chemistry
Issue number4
StatePublished - Jul 2007

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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