Smart copolymer coated SPIONs for colon cancer chemotherapy

Abstract

Human colon cancer is one of the higher aggressive solid tumors, whose high mortality, much like many other solid tumors, results from metastasis formation. To reduce this high mortality, more effective chemotherapy, allowing a specific tumor accumulation and an efficient early-stage medical imaging as well, are still needed. At this regard, stimuli-responsive nanocarriers for anticancer drug delivery are promising strategy in cancer therapy. For this purpose, a dual targeted redox-responsive drug delivery system, prepared by coating superparamagnetic nanoparticles (SPIONs) with the amphiphilic copolymer INU-LA-PEG-FA and loading doxorubicin (DOXO-SPIONs) was investigated as tool for solid tumor chemotherapy. Folic acid (FA) has been chosen as active targeting agent as its receptor is upregulated in many tumors, including colon cancer. Lipoic acid (LA) has been used to act as the redox-responsive moiety, due to the presence of the -S-S- linkage into its structure, which can undergo intracellular reductive-induced cleavage, and therefore, a modification of stability and release profile of the nanocarrier. Accumulation by magnetic attraction was used as synergistic targeting strategy. Improved anticancer activity was demonstrated in mice by evaluating tumor volume reduction, immunohistochemical analyses and imaging properties using magnetic resonance imaging (MRI).