Folic Acid-Conjugated Magnetic Oleoyl-Chitosan Nanoparticles for Controlled Release of Doxorubicin in Cancer Therapy

To develop an efficient drug delivery system, we co-entrapped superparamagnetic Fe₃O₄ and the chemotherapeutic drug doxorubicin (DOX) in oleoyl-chitosan (OC) to prepare DOX-entrapped magnetic OC (DOX-MOC) nanoparticles (NPs) through ionic gelation of OC with sodium tripolyphosphate (TPP). The NPs provide magnetically targeted delivery of DOX in cancer therapy. Using folic acid (FA)-grafted OC, FA-conjugated DOX-entrapped magnetic OC (FA-DOX-MOC) NPs were prepared similarly for FA-mediated active targeting of cancer cells with overexpressed folate receptors. Considering DOX loading and release, the best conditions for preparing DOX-MOC NPs were an OC:TPP mass ratio = 1:4 and OC concentration = 0.2%. These spherical NPs had a particle size of ~250 nm, 87.9% Fe₃O₄ content, 53.1 emu/g saturation magnetization, 83.1% drug encapsulation efficacy, and 2.81% drug loading efficiency. FA did not significantly change the physico-chemical characteristics of FA-DOX-MOC compared to DOX-MOC, and both NPs showed pH-dependent drug release behaviors, with much faster release of DOX at acidic pH values found in endosomes. However, FA could enhance the intracellular uptake of the NPs and DOX accumulation in the nucleus. This active targeting effect led to significantly higher cytotoxicity towards U87 cancer cells. These results suggest that FA-DOX-MOC NPs can efficiently deliver DOX for controlled drug release in cancer therapy.