Temperature-sensitive polymer-coated magnetic nanoparticles as a potential drug delivery system for targeted therapy of thyroid cancer.

The objective of this work was to develop and investigate temperature-sensitive poly(N-isopropylacrylamide-acrylamide-allylamine)-coated iron oxide magnetic nanoparticles (TPMNPs) as possible targeted drug carriers for treatments of advanced thyroid cancer (ATC). These nanoparticles were prepared by free radical polymerization of monomers on the surface of silane-coupled iron oxide nanoparticles. In vitro studies demonstrated that TPMNPs were cytocompatible and effectively taken up by cancer cells in a dose-dependent manner. An external magnetic field significantly increased nanoparticle uptake, especially when cells were exposed to physiological flow conditions. Drug loading and release studies using doxorubicin confirmed the temperature-responsive release of drugs from nanoparticles. In addition, doxorubicin-loaded nanoparticles significantly killed ATC cells when compared to free doxorubicin. The in vitro results indicate that TPMNPs have potential as targeted and controlled drug carriers for thyroid cancer treatment.

Multifunctional particles for melanoma-targeted drug delivery.

New magnetic-based core-shell particles (MBCSPs) were developed to target skin cancer cells while delivering chemotherapeutic drugs in a controlled fashion. MBCSPs consist of a thermo-responsive shell of poly(N-isopropylacrylamide-acrylamide-allylamine) and a core of poly(lactic-co-glycolic acid) (PLGA) embedded with magnetite nanoparticles. To target melanoma cancer cells, MBCSPs were conjugated with Gly-Arg-Gly-Asp-Ser (GRGDS) peptides that specifically bind to the α(5)ß(3) receptors of melanoma cells. MBCSPs consist of unique multifunctional and controlled drug delivery characteristics. Specially, they can provide dual drug release mechanisms (a sustained release of drugs through degradation of PLGA core and a controlled release in response to changes in temperature via thermo-responsive polymer shell), and dual targeting mechanisms (magnetic localization and receptor-mediated targeting). Results from in vitro studies indicate that GRGDS-conjugated MBCSPs have an average diameter of 296 nm and exhibit no cytotoxicity towards human dermal fibroblasts up to 500 µg ml(-1). Further, a sustained release of curcumin from the core and a temperature-dependent release of doxorubicin from the shell of MBCSPs were observed. The particles also produced a dark contrast signal in magnetic resonance imaging. Finally, the particles were accumulated at the tumor site in a B16F10 melanoma orthotopic mouse model, especially in the presence of a magnet. Results indicate great potential of MBCSPs as a platform technology to target, treat and monitor melanoma for targeted drug delivery to reduce side effects of chemotherapeutic reagents.