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

Abstract

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.

Selection of potential iron oxide nanoparticles for breast cancer treatment based on in vitro cytotoxicity and cellular uptake

“…Dex showed a much weaker magnetization course, most likely caused by the relatively small particle core size. 30 To further characterize the nanoparticles, we investigated the surface properties and particle size, as these parameters play a key role in determining the nanoparticle-cell interactions. 31 The surface properties are usually altered by the presence of proteins in the solvent, which leads to the formation of a complex dynamic corona that can influence nanoparticle stability, uptake and toxicity.…”

Hypericin-bearing magnetic iron oxide nanoparticles for selective drug delivery in photodynamic therapy

“…26 In brief, an aqueous solution containing 8.8% (w/w) dextran, 2.4% (w/w) FeCl 3 ⋅6H 2 O, and 0.9% (w/w) FeCl 2 ⋅4H 2 O was prepared and filtered through a 0.22-µm membrane into an ice-cooled three-neck round-bottomed flask. Under an argon atmosphere, the temperature was adjusted to 0°C-4°C.…”

Non-immunogenic dextran-coated superparamagnetic iron oxide nanoparticles: a biocompatible, size-tunable contrast agent for magnetic resonance imaging

“…Furthermore, the stabilization of the dextran coating by a crosslinking process ensures that the coating is continuous, thus preventing the exposure of the iron core to serum proteins. Following the extensive physicochemical and magnetic characterization of SPIONdex particles, 30,31 we now investigated the key parameters related to their hemocompatibility and immunosafety. To address concerns associated with hypersensitivity reactions to injectable nanoparticulate agents, we tested whether intravenous administration of SPIONdex induces complement activation-related pseudoallergy (CARPA) in pigs.…”