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.

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