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

摘要

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 (SPIODOX-PPLVs) as a novel theranostic system for tumor magnetic resonance imaging (MRI) diagnosis and controlled drug delivery. These SPIODOX-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 SPIODOX-PPLVs have nanosized structures (similar to 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 SPIODOX-PPLVs is accelerated in the reduction environment. An in vitro cellular uptake study and an antitumor study show that the SPIODOX-PPLVs have magnetic targeting properties and effective antitumor activity. In vivo studies show the SPIODOX-PPLVs have excellent T-2-weighted tumor targeted MRI capability, image-guided drug delivery capability, and high antitumor effects. These results suggest that the SPIODOX-PPLVs are promising nanocarriers for MRI diagnosis and cancer therapy applications.