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Innovation in synthesis of natural based Superparamagnetic nanocomposite with large pore mesoporous Hydroxyapatite as a coating for Fe3O4 nanoparticles.The synthesized nanoparticle could act as a carrier for doxorubicin with loading efficiency of 93% which is a high value compared with other reports.No significant differences on cellular viability of SKBR3 and T47D cells were observed after incubation of the cell lines with free doxorubicin or the synthesized mesoporous Hydroxyapatite coated superparamagnetic Fe3O4 nanoparticles loaded with doxorubicin.As a superparamagnetic nanoparticle, this platform could be of use in magnetically assisted drug delivery, MRI, hyperthermia and tissue engineering.In the present study, a series of multifunctional drug delivery systems based on mesostructured hydroxyapatite coating and superparamagnetic nanoparticles with pH-responsive characters was prepared. The structure of each new synthesized nanoscale composite was fully characterized by XRD, FTIR, TEM, VSM and BET. The results showed a good ordered mesostructure having large pores, high pore volume, high surface area, and varied super paramagnetic properties. The mesoporous hydroxyapatite coated super paramagnetic Fe3O4 nanoparticles were applied as a drug delivery carrier loaded with doxorubicin (DOX) as a model drug. The storage/release properties of the developed nonocarriers in phosphate buffer saline (PBS) were studied in two certain pHs: pH = 7.4 (the human blood pH) and pH = 5.5 (pH of cancer cells). The large pores in the synthesized mesoporous acted as an excellent carrier for DOX molecules with a loading efficiency of ≈93% which is much higher than that of the conventional hydroxyapatite particles. When the pH of the release medium (PBS) was changed from 7.4 to 5.5, the drug release increased significantly from 10% of the adsorbed drug to about 70%. DOX-loaded mesostructure hydroxyapatite reduced the viability of SKBR3 and T47D cells by 54.7 and 57.3%, respectively, which were very similar to 56.8 and 60.4% reduction resulted from free DOX incubation. This new drug delivery system which benefits from both super paramagnetic properties and pH-responsive performances may serve as a suitable platform for developing new biocompatible drug carriers and could have a good potential use in targeted cancer therapy.