pH-Responsible Doxorubicin-Loaded Fe₃O₄@CaCO₃ Nanocomposites for Cancer Treatment

A magnetic nanocomposite (MNC) is an integrated nanoplatform that combines a set of functions of two types of materials. A successful combination can give rise to a completely new material with unique physical, chemical, and biological properties. The magnetic core of MNC provides the possibility of magnetic resonance or magnetic particle imaging, magnetic field-influenced targeted delivery, hyperthermia, and other outstanding applications. Recently, MNC gained attention for external magnetic field-guided specific delivery to cancer tissue. Further, drug loading enhancement, construction stability, and biocompatibility improvement may lead to high progress in the area. Herein, the novel method for nanoscale Fe₃O₄@CaCO₃ composites synthesis was proposed. For the procedure, oleic acid-modified Fe₃O₄ nanoparticles were coated with porous CaCO₃ using an ion coprecipitation technique. PEG-2000, Tween 20, and DMEM cell media was successfully used as a stabilization agent and template for Fe₃O₄@CaCO₃ synthesis. Transmission electron microscopy (TEM), Fourier transform infrared (FTIR) spectroscopy, and dynamic light scattering (DLS) data were used for the Fe₃O₄@CaCO₃ MNC's characterization. To improve the nanocomposite properties, the concentration of the magnetic core was varied, yielding optimal size, polydispersity, and aggregation ability. The resulting Fe₃O₄@CaCO₃ had a size of 135 nm with narrow size distributions, which is suitable for biomedical applications. The stability experiment in various pH, cell media, and fetal bovine serum was also evaluated. The material showed low cytotoxicity and high biocompatibility. An excellent anticancer drug doxorubicin (DOX) loading of up to 1900 µg/mg (DOX/MNC) was demonstrated. The Fe₃O₄@CaCO₃/DOX displayed high stability at neutral pH and efficient acid-responsive drug release. The series of DOX-loaded Fe₃O₄@CaCO₃ MNCs indicated effective inhibition of Hela and MCF-7 cell lines, and the IC 50 values were calculated. Moreover, 1.5 μg of the DOX-loaded Fe₃O₄@CaCO₃ nanocomposite is sufficient to inhibit 50% of Hela cells, which shows a high prospect for cancer treatment. The stability experiments for DOX-loaded Fe₃O₄@CaCO₃ in human serum albumin solution indicated the drug release due to the formation of a protein corona. The presented experiment showed the "pitfalls" of DOX-loaded nanocomposites and provided step-by-step guidance on efficient, smart, anticancer nanoconstruction fabrication. Thus, the Fe₃O₄@CaCO₃ nanoplatform exhibits good performance in the cancer treatment area.