Folic acid-coupled bovine serum albumin-modified magnetic nanocomposites from quantum-sized Fe3O4 and layered double hydroxide for actively targeted delivery of 5-fluorouracil

The development of multifunctional magnetic nanocomposites as a drug delivery system for Cancer therapy is highly desirable in current nanomedicine. Herein, folic acid-bovine serum albumin conjugate (FA-BSA) was modified on nanocomposites by combining quantum-sized Fe₃O₄ and layered double hydroxide (LDH) to obtain a novel FA-BSA/Fe₃O₄@LDH for the delivery of the Anticancer drug 5-Fluorouracil (5-Fu). The prepared nanocomposites showed good dispersibility, colloidal stability, magnetic property and erythrocyte compatibility. FA-BSA/Fe₃O₄@LDH/5-Fu showed pH responsiveness, with both the amount and duration of release of FA-BSA/Fe₃O₄@LDH/5-Fu being significantly higher in pH 5.0 release medium than in pH 7.4 release medium. The cellular experiments implied that no significant cytotoxicity of FA-BSA/Fe₃O₄@LDH, particularly due to the presence of FA-BSA, which further enhanced the biocompatibility of the nanocomposite. Furthermore, FA-BSA/Fe₃O₄@LDH/5-Fu could specifically target the 2D HepG2 cells model and 3D hepatoma cell microspheres model in vitro, and efficient internalization through folate receptor-mediated endocytosis, showing excellent anti-cancer cell activity in a concentration-dependent manner. Therefore, the constructed FA-BSA/Fe₃O₄@LDH was able to provide a potential novel multifunctional nanocomposite for magnetic-targeting drug delivery and pH-responsive release of drugs to enhance the efficiency of Cancer therapy.

Hepatocellular carcinoma; Layered double hydroxide (LDH); Magnetic nanocomposites; Targeted delivery system; pH-responsive.