SCHEDULED MAINTENANCE
Design and synthesis of aptamer AS1411-conjugated EG@TiO2@Fe2O3 nanoparticles as a drug delivery platform for tumor-targeted therapy
Abstract
Nucleolin, an RNA binding protein, is considered to be a target for developing cancer therapies and diagnostics. Herein, we have reported a designed nucleolin-targeted AS1411 aptamer conjugated to guanidinium groups of epibromohydrin functionalized TiO2@γ-Fe2O3 nanoparticles (AS1411@GMBS@EG@TiO2@Fe2O3, NP–Apt) to increase drug delivery in targeted tumor tissues. The structure and morphology of the obtained NPs were characterized by FT-IR, VSM, EDX, HRTEM, and TEM analysis. Doxorubicin (DOX) was entrapped in NP–Apt (NP–Apt–DOX) with an entrapment efficiency of 47.59 ± 3.98%. NP–Apt–DOX revealed homogeneous characteristics with narrow particle size distributions. The in vitro drug release of NP–Apt–DOX was pH-dependent with initial rapid release (within 6 h) followed by sustained release for 72 h. Fluorescence microscopy and MTT assay were used to assess the cellular uptake and anti-proliferation activity of NP–Apt–DOX against nucleolin-positive (A375 and C26) cells. NP–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 were observed in mice bearing C26 colon carcinoma treated with NP–Apt–DOX. Overall, AS1411@GMBS@EG@TiO2@Fe2O3 is a pH-responsive sustained release system and offers promise as an effective and safe system for targeted drug delivery.
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