Tissue Plasminogen Activator Binding to Superparamagnetic Iron Oxide Nanoparticle-Covalent Versus Adsorptive Approach

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Details zur Publikation

Autorinnen und Autoren: Friedrich RP, Zaloga J, Schreiber E, Toth IY, Tombacz E, Lyer S, Alexiou C
Zeitschrift: Nanoscale Research Letters
Jahr der Veröffentlichung: 2016
Band: 11
Heftnummer: 1
ISSN: 1931-7573
eISSN: 1556-276X


Functionalized superparamagnetic iron oxide nanoparticles are frequently used to develop vehicles for drug delivery, hyperthermia, and photodynamic therapy and as tools used for magnetic separation and purification of proteins or for biomolecular imaging. Depending on the application, there are various possible covalent and non-covalent approaches for the functionalization of particles, each of them shows different advantages and disadvantages for drug release and activity at the desired location.Particularly important for the production of adsorptive and covalent bound drugs to nanoparticles is the pureness of the involved formulation. Especially the covalent binding strategy demands defined chemistry of the drug, which is stabilized by excess free amino acids which could reduce reaction efficiency. In this study, we therefore used tangential flow filtration (TFF) method to purify the drugs before the reaction and used the frequently applied and clinically available recombinant tissue plasminogen activator (tPA; Actilyse(®)) as a proof of concept. We then coupled the tPA preparation to polyacrylic acid-co-maleic acid (PAM)-coated superparamagnetic iron oxide nanoparticles (SPIONs) using an amino-reactive activated ester reaction and compared these particles to PAM-coated SPIONs with electrostatically adsorbed tPA.Using dynamic light scattering (DLS) and pH-dependent electrokinetic mobility measurements, we showed that surface properties of the SPIONs were significantly greater affected after activation of the particles compared to the adsorption controls. Different in vitro assays were used to investigate the activity of tPA after coupling to the particles and purification of the ferrofluid. Covalent linkage significantly improves the reactivity and long-term stability of the conjugated SPION-tPA system compared to simple adsorption. In conclusion, we have shown an effective way to produce SPIONs with covalent and non-covalent ultra-filtrated drugs. We showed that using activated ester reaction, immobilization of the protein was significantly better than in adsorptive approaches. Investigation of those functionalized SPIONs revealed diverging attributes, which should be taken into account when developing nanoparticles for different applications.

FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Alexiou, Christoph Prof. Dr.
Professur für Nanomedizin
Lyer, Stefan Dr. rer. nat.
Hals-Nasen-Ohren-Klinik - Kopf- und Halschirurgie
Zaloga, Jan Dr. rer. nat.
Hals-Nasen-Ohren-Klinik - Kopf- und Halschirurgie

Einrichtungen weiterer Autorinnen und Autoren

University of Szeged / József Attila Tudományegyetem Szeged


Friedrich, R.P., Zaloga, J., Schreiber, E., Toth, I.Y., Tombacz, E., Lyer, S., & Alexiou, C. (2016). Tissue Plasminogen Activator Binding to Superparamagnetic Iron Oxide Nanoparticle-Covalent Versus Adsorptive Approach. Nanoscale Research Letters, 11(1). https://dx.doi.org/10.1186/s11671-016-1521-7

Friedrich, Ralf P., et al. "Tissue Plasminogen Activator Binding to Superparamagnetic Iron Oxide Nanoparticle-Covalent Versus Adsorptive Approach." Nanoscale Research Letters 11.1 (2016).


Zuletzt aktualisiert 2018-22-10 um 14:53