Vol.:(0123456789) Research on Chemical Intermediates https://doi.org/10.1007/s11164-020-04205-9 1 3 Investigation of controlled release properties and anticancer effect of folic acid conjugated magnetic core–shell nanoparticles as a dual responsive drug delivery system on A‑549 and A‑431 cancer cell lines Nahid Shahabadi 1,2  · Mahtab Razlansari 1  · Aref Khorshidi 1  · Hossein Zhaleh 3 Received: 18 April 2020 / Accepted: 26 June 2020 © Springer Nature B.V. 2020 Abstract Epirubicin loaded on magnetite-coated calcium ferrite conjugated folic acid (Fe 3 O 4 @CaFe 2 O 4 -FA@EPI) was synthesized and characterized using various tech- niques like SEM, EDX, FT-IR, XRD, TGA, BET, and VSM. Also, the therapeu- tic effects on A-549 and A-431 cancer cell lines and delivering ability of Fe 3 O 4 @ CaFe 2 O 4 -FA@EPI for potential use as a system of targeted drug delivery in cancer therapy were investigated. The obtained results show that these hybrid nanoscale particles have a large capacity of adsorption for EPI (19.4 wt.%) and desirable drug loading performance (97.5%). The acetate buffer environment guides the drug release to a higher amount (99%), in comparison with the phosphate-buffered saline (28%). Also, the Fe 3 O 4 @CaFe 2 O 4 -FA@EPI nanohybrids in vitro cytotoxic activity versus A-549 (null folate receptor) and A-431 (positive folate receptor) cancer cell lines in group III (Fe 3 O 4 @EPI) investigations, show the higher cell cytotoxicity and apoptosis in A-549 cells compared to A-431 (p < 0.05). Moreover, in A-431 cells, the percent of cell cytotoxicity and cell death grew in the Fe 3 O 4 @CaFe 2 O 4 -FA@EPI group in comparison with the A-549 cell line (p < 0.05). The results illustrated the effects of Fe 3 O 4 @CaFe 2 O 4 -FA@EPI group on cytotoxicity and apoptosis of A-431 positive folate receptor cancer cells were almost two times greater than free EPI. Furthermore, obtained findings show that the Fe 3 O 4 @CaFe 2 O 4 -FA@EPI provides a specific growth inhibition of cancer cells through binding to receptors on the cell membrane and intracellular uptake. Keywords Calcium ferrite · Folic acid · Epirubicin · pH-responsive · Targeted drug delivery * Nahid Shahabadi NahidShahabadi@yahoo.com Extended author information available on the last page of the article