Multifunctional reduction-responsive SPIO and DOX-loaded PEGylated polymeric lipid vesicles for magnetic resonance imaging-guided drug delivery

Multifunctional superparamagnetic iron-oxide (SPIO)-based nanoparticles have been emerging as candidate nanosystems for cancer diagnosis and therapy. Here, we report the use of reduction- responsive SPIO/doxorubicin (DOX)-loaded poly(ethylene glycol) monomethyl ether (PEG)ylated polymeric lipid vesicles (SPIO and DOX-PPLVs) as a novel theranostic system for tumor magnetic resonance imaging (MRI) diagnosis and controlled drug delivery. These SPIO and DOX-PPLVs are composed of SPIOs that function as MR contrast agents for tumor enhancement and PPLVs as polymer matrices for encapsulating SPIO and antitumor drugs. The in vitro characterizations show that the SPIO and DOX-PPLVs have nanosized structures (∼80 nm), excellent colloidal stability, good biocompatibility, as well as T ₂-weighted MRI capability with a relatively high T ₂ relaxivity (r ₂ = 213.82 mM⁻¹ s⁻¹). In vitro drug release studies reveal that the release rate of DOX from the SPIO and DOX-PPLVs is accelerated in the reduction environment. An in vitro cellular uptake study and an antitumor study show that the SPIO and DOX-PPLVs have magnetic targeting properties and effective antitumor activity. In vivo studies show the SPIO and DOX-PPLVs have excellent T ₂-weighted tumor targeted MRI capability, image-guided drug delivery capability, and high antitumor effects. These results suggest that the SPIO and DOX-PPLVs are promising nanocarriers for MRI diagnosis and cancer therapy applications. (paper)