Development and characterization of magnetic iron oxide nanoparticles with a cisplatin-bearing polymer coating for targeted drug delivery

• Published in: International journal of nanomedicine Vol. 9; no. Issue 1; pp. 3659 - 3676
• Main Authors: Unterweger, Harald, Tietze, Rainer, Janko, Christina, Zaloga, Jan, Lyer, Stefan, Dürr, Stephan, Taccardi, Nicola, Goudouri, Ourania-Menti, Hoppe, Alexander, Eberbeck, Dietmar, Schubert, Dirk W, Boccaccini, Aldo R, Alexiou, Christoph
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2014; Taylor & Francis Ltd; Dove Press; Dove Medical Press
• Subjects: Cancer; Cell adhesion & migration; Cell Death - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Cellulose; Cisplatin; Cisplatin - chemistry; Cisplatin - pharmacokinetics; Cisplatin - pharmacology; Complications and side effects; Deoxyribonucleic acid; dextran; Dextrans - chemistry; DNA; Dosage and administration; Drug Carriers - chemistry; Drug Delivery Systems; Drugs; Engineering; Flow cytometry; Health aspects; Humans; hyaluronic acid; Hyaluronic Acid - chemistry; Jurkat Cells; magnetic drug targeting; Magnetite Nanoparticles - chemistry; Materials science; Molecular weight; Nanoparticles; NMR; Nuclear magnetic resonance; Original Research; Particle Size; Physiological aspects; Polymers; Properties; superparamagnetic iron oxide nanoparticles; Tumors; Vehicles; Germany; United States > US; dextran; magnetic drug targeting; superparamagnetic iron oxide nanoparticles; hyaluronic acid
• ISSN: 1178-2013; 1176-9114; 1178-2013
• DOI: 10.2147/IJN.S63433

A highly selective and efficient cancer therapy can be achieved using magnetically directed superparamagnetic iron oxide nanoparticles (SPIONs) bearing a sufficient amount of the therapeutic agent. In this project, SPIONs with a dextran and cisplatin-bearing hyaluronic acid coating were successfully synthesized as a novel cisplatin drug delivery system. Transmission electron microscopy images as well as X-ray diffraction analysis showed that the individual magnetite particles were around 4.5 nm in size and monocrystalline. The small crystallite sizes led to the superparamagnetic behavior of the particles, which was exemplified in their magnetization curves, acquired using superconducting quantum interference device measurements. Hyaluronic acid was bound to the initially dextran-coated SPIONs by esterification. The resulting amide bond linkage was verified using Fourier transform infrared spectroscopy. The additional polymer layer increased the vehicle size from 22 nm to 56 nm, with a hyaluronic acid to dextran to magnetite weight ratio of 51:29:20. A maximum payload of 330 μg cisplatin/mL nanoparticle suspension was achieved, thus the particle size was further increased to around 77 nm with a zeta potential of -45 mV. No signs of particle precipitation were observed over a period of at least 8 weeks. Analysis of drug-release kinetics using the dialysis tube method revealed that these were driven by inverse ligand substitution and diffusion through the polymer shell as well as enzymatic degradation of hyaluronic acid. The biological activity of the particles was investigated in a nonadherent Jurkat cell line using flow cytometry. Further, cell viability and proliferation was examined in an adherent PC-3 cell line using xCELLigence analysis. Both tests demonstrated that particles without cisplatin were biocompatible with these cells, whereas particles with the drug induced apoptosis in a dose-dependent manner, with secondary necrosis after prolonged incubation. In conclusion, combination of dextran-coated SPIONs with hyaluronic acid and cisplatin represents a promising approach for magnetic drug targeting in the treatment of cancer.