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

Graphical abstract Highlights • Fe 3 O 4 NPs conjugated with DOX, PEG, and folic acid were developed. • The amount of DOX released from the NPs was higher at pH 5.6 than pH 7.4. • The NPs showed the higher cellular uptake due to the presence of folic acid. • The NPs showed an enhanced cytotoxicity against the HeLa cells. • The transverse relaxivity (r 2 ) of the NPs was 133 mM−1S−1. 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-OCH 3 /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-OCH 3 /FA nanocarriers was determined as 14 and 40 nm by TEM and DLS, respectively. The saturation magnetization (Ms) and transverse relaxivity (r 2 ) value of IO-MMA-DOX-PEG-OCH 3 /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-OCH 3 /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-OCH 3 /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-OCH 3 /FA nanocarriers could be promising for cancer therapy with the improved drug loading, tumor-targeted controlled drug release and MRI abilities. [ABSTRACT FROM AUTHOR]