Doxorubicin Folic Acid-Chitosan Conjugate-Based Super Paramagnetic Erythrocyte-Loaded Nano Delivery System as Onco-theranostic Platform

Doxorubicin (DOX) is a broad-spectrum antineoplastic agent that is used in hepatocellular carcinoma (HCC) treatment regimens. In this study, DOX was loaded in folic acid (FA)-chitosan (Cs) conjugate-coated superparamagnetic iron oxide nanoparticles (SPIONs) (DOX@FA-Cs/SPIONs) and then further encapsulated within erythrocytes to act as a liver-specific onco-theranostic system for HCC management. In this regard, SPIONs were prepared through the co-precipitation technique. The particle size and morphology of the prepared SPIONs were assessed through transmission electron microscopy (TEM). Then, FA and Cs were conjugated through a chemical bond and were characterized through the FTIR and 1 H NMR spectrum. After that, FA-Cs conjugate was used to coat SPIONs, and finally, DOX was loaded and DOX@FA-Cs/SPIONs were stabilized by the ionic gelation technique using sodium tripolyphosphate (TPP) as cross-linker. Particle size and morphology, zeta potential, drug loading, drug release, and paramagnetic behavior of the particles were assessed in the optimized formulation. Finally, the prepared DOX nanoparticles were further encapsulated in erythrocytes, and they were optimized and characterized. FTIR and 1 H NMR spectrum confirmed the FA-Cs conjugate formation. TEM results revealed that DOX@FA-Cs/SPIONs were spherical in shape with an average diameter of ~ 20 nm, and their zeta potential was + 15.3 mV. The results revealed that the entrapment efficiency and loading capacity of DOX within FA-Cs/SPIONs were 36.0 ± 1.5% and 11.8 ± 0.5%, respectively. The results of the drug release revealed a much higher and faster release rate in acidic pH. Vibrating sample magnetometry results revealed the preserved superparamagnetic properties of FA-Cs/SPIONs. Encapsulation of DOX@FA-Cs/SPIONs within erythrocytes was accompanied by a high entrapment efficiency of 57 ± 2% and could preserve their magnetic properties. This novel DOX delivery system would be a promising liver-specific onco-theranostic system for HCC management. Graphical abstract