Abstract
Cancer hyperthermia induced through magnetic nanoparticles that generate heat upon irradiation with an alternating magnetic field (AMF) allows local heating of tumor tissues, leading to cancer cell death. For the clinical application of magnetic nanoparticles, designing an appropriate surface structure is important for maintaining colloidal stability and stealth properties that prevent clearance by the mononuclear phagocyte system. Catechol-containing polymers offer stable modification and functionalization of nanoparticles. However, the effect of their molecular structure on the modification efficiency and function of nanoparticles remains unclear. Herein, magnetite nanoparticles (MNPs) modified with a series of catechol-containing polymers composed of dopamine methacrylamide (DMA) units and biocompatible phosphorylcholine units were prepared. Higher molecular weights of the polymers resulted in higher modification amounts on the MNPs, whereas the DMA unit content had little impact. Modifying the polymers improved the dispersion stability of the MNPs in phosphate-buffered saline and their stealth property against macrophages in vitro. Polymers with more than 1.8 mol % DMA units enabled stable dispersion of MNPs for 14 days. Modifying the polymers with DMA unit contents between 4.8 and 9.0 mol % minimized the macrophage uptake of the MNPs. Moreover, the polymer-modified MNPs were loaded with the anticancer drug bortezomib, and the release of bortezomib was enhanced by irradiation with an AMF for magnetic hyperthermia. In vitro magnetic hyperthermia with polymer-modified MNPs successfully killed mouse colon cancer cells, and bortezomib loading augmented the anticancer activity. This study will provide crucial guidance on the molecular design of catechol-containing polymers for effective cancer hyperthermia using magnetic nanoparticles.