Design and synthesis of aptamer AS1411-conjugated EG@TiO2@Fe2O3 nanoparticles as a drug delivery platform for tumor-targeted therapy

Nucleolin, an RNA binding protein, is considered to be a target for developing cancer therapies and diagnostics. Herein, we report a designed nucleolin-targeted AS1411 aptamer conjugated to guanidinium groups of epibromohydrin functionalized TiO2@γ-Fe2O3 nanoparticles (AS1411@EG@TiO2@Fe2O3, NPs-Apt) to increase drug delivery in targeted tumor tissues. The structure and morphology of obtained NPs were characterized by FT-IR, XRD, EDX, VSM, and HR-TEM methods. Doxorubicin (DOX) was entrapped in NPs-Apt (NPs-Apt-DOX) with entrapment efficiency of 47.59 ± 3.98%. NPs-Apt-DOX revealed homogeneous characteristics with narrow particle size distributions. In vitro drug release of NPs-Apt-DOX was pH-dependent with an initial rapid release (within 6 h) followed by a sustained release for 72 h. Fluorescence microscopy and MTT assay were used to assess the cellular uptake and anti-proliferation activity of NPs-Apt-DOX against nucleolin-positive (A375 and C26) cells. NPs-Apt-DOX showed higher cellular uptake and more enhanced cytotoxicity in nucleolin-expressing cancer cells than in L929 fibroblasts as a nucleolin-negative cell line through increasing intracellular ROS levels. Significant tumor growth inhibition and prolonged animal survival was observed in mice bearing C26 colon carcinoma treated with NPs-Apt-DOX. Overall, AS1411@EG@TiO2@Fe2O3 is a pH-responsive sustained release system and offers promise as an effective and a safe system for targeted drug delivery.