Multi-functional nanocarriers based on iron oxide nanoparticles conjugated with doxorubicin, poly(ethylene glycol) and folic acid as theranostics for cancer therapy

Abstract

Multi-functional nanocarriers based on iron oxide nanoparticles (IONPs) conjugated with doxorubicin (DOX), poly(ethylene glycol) (PEG), and folic acid (FA) (IO-MMA-DOX-PEG-OCH₃/FA) were prepared as theranostics for cancer therapy. Using mono-methyl adipate (MMA) as a linker, the anticancer drug, DOX, was conjugated on the surface of IONPs by acid-cleavable hydrazone bond. The average size of the IO-MMA-DOX-PEG-OCH₃/FA nanocarriers was determined as 14 and 40 nm by TEM and DLS, respectively. The saturation magnetization (Ms) and transverse relaxivity (r₂) value of IO-MMA-DOX-PEG-OCH₃/FA nanocarriers were calculated as 28.62 Am²/kg and 133 mM^-1s^-1, respectively. The rate and amount of DOX released from the IO-MMA-DOX-PEG-OCH₃/FA nanocarriers were higher at acidic medium (pH 5.6) than that at alkaline medium (pH 7.4) due to the presence of hydrazone bond between the DOX and IONPs. The IO-MMA-DOX-PEG-OCH₃/FA nanocarriers showed the higher cellular uptake than FA-free nanocarriers due to the folate-receptor-mediated endocytosis, thereby presenting an enhanced cytotoxicity against folate-receptor-positive HeLa cells through apoptosis. The results confirmed that the IO-MMA-DOX-PEG-OCH₃/FA nanocarriers could be promising for cancer therapy with the improved drug loading, tumor-targeted controlled drug release and MRI abilities.

Keywords: Drug delivery; Multi-functional; Nanocarriers; Theranostics; Tumor-targeted.