Targeted tumor drug delivery and magnetic hyperthermia for cancer treatment by chemotherapeutic-conjugated magnetic nanoparticles

Abstract

One of the promising strategies for improvement of cancer treatment is based on magnetic drug delivery systems, thus avoiding side effects of standard chemotherapies. Superparamagnetic iron oxide (SPIONs) nanoparticles have ideal properties to become a targeted magnetic drug delivery contrast probes, named theranostics. The aim of this work was to investigate the in vitro effect of the loading of doxorubicin (DOX) on negatively charged polycarboxylic iron-oxide nanoparticles (SPIONs) on breast carcinoma cell lines. For proper analysis and understanding of cell behavior after administration of DOX-SPIONs compared with free DOX, a complex set of in vitro tests, including production of MTT assay, cell cycle determination, and cellular uptake, were utilized. In summary, we have developed a magnetic nanoparticle-based drug delivery system that sequentially delivers the cytotoxic drug doxorubicin to breast cancer cells (MCF-7 and MDA-MB-231). The drug-coated nanoparticles, DOX-NPs, were assembled stepwise, with doxorubicin adsorbed to bare iron oxide nanoparticles first, by electrostatic reaction and allowed for the complexation of doxorubicin. DOX-NPs were stable in solution at 37 °C and physiological pH (7.4). Rapid in vitro release of doxorubicin followed by gradual release of doxorubicin was triggered in aqueous solution by low pH (5.4) and heating. As a result of minimal internalization, the particles were not significantly toxic to noncancerous cells (MCF-10A). In contrast, they were internalized to a much greater extent in MCF-7 and MDA-MB-231 cells and were cytotoxic due to the synergistic action of the two drugs and the effects of hyperthermia. The drug-coated particles were able to inhibit growth and proliferation of breast cancer cells in vitro, indicating that the system has potential to act as an antimetastatic chemothermotherapeutic agent.One of the promising strategies for improvement of cancer treatment is based on magnetic drug delivery systems, thus avoiding side effects of standard chemotherapies. Superparamagnetic iron oxide (SPIONs) nanoparticles have ideal properties to become a targeted magnetic drug delivery contrast probes, named theranostics. The aim of this work was to investigate the in vitro effect of the loading of doxorubicin (DOX) on negatively charged polycarboxylic iron-oxide nanoparticles (SPIONs) on breast carcinoma cell lines. For proper analysis and understanding of cell behavior after administration of DOX-SPIONs compared with free DOX, a complex set of in vitro tests, including production of MTT assay, cell cycle determination, and cellular uptake, were utilized. In summary, we have developed a magnetic nanoparticle-based drug delivery system that sequentially delivers the cytotoxic drug doxorubicin to breast cancer cells (MCF-7 and MDA-MB-231). The drug-coated nanoparticles, DOX-NPs, were assembled stepwise, with...