Mesoporous superparamagnetic hydroxyapatite nanocomposite: A multifunctional platform for synergistic targeted chemo-magnetotherapy

Abstract

In the present study, the aim was to develop a magneto-responsive nanocomposite for application in drug delivery by the integration of magnetic nanoparticles into an inorganic architecture, hydroxyapatite. The magnetic mesoporous hydroxyapatite nanocomposites, MMHAPs, were synthesized using a template-free method and fully characterized by XRD, FT-IR, TEM, FE-SEM, VSM, ICP, BET, and UV–Vis spectroscopy. MMHAPs exhibited a rod-like shape with a structure of large mesopores and high surface area. A sample of the nanocomposites with well-defined properties, MMHAP(2), was selected as a carrier for delivery of chemotherapy drug, doxorubicin (Dox). Then, it was coated with polyethylene glycol (P) and folic acid (F), providing aqueous stability and tumor targeting, respectively. The evaluation of drug release profile revealed that the release of drug occurs in a time-staggered manner under low pH conditions, which simulate the internal condition of lysosome. More important, a significant drug release was observed under a static magnetic field (SMF), displaying a magnetically triggered release. According to the toxicity assessment, MMHAP(2) did not show any noticeable toxic effect against the tumor cells (Saos-2) and normal cells (HEK-293) up to 100 μg ml−1 in the presence or absence of SMF. In contrast, the drug-loaded nanocomposite, F.P.D@MMHAP(2), possesses high antitumor efficacy particularly in the presence of SMF. Moreover, it was found that the cellular internalization of F.P.D@MMHAP(2) could be increased by SMF, providing therapeutic efficiency enhancement. The high cytotoxic effect of F.P.D@MMHAP(2) with the help of SMF caused apoptosis in the tumor cells, which was preceded by a disturbance in the intracellular redox state and then caspase activation. Based on the data obtained, F.P.D@MMHAP(2) is a pH- and magneto-responsive platform opening up a new perspective in terms of its exploitation in cancer therapy.