Transferrin-conjugated drug/dye-co-encapsulated magnetic nanocarriers for active-targeting fluorescent/magnetic resonance imaging and anti-tumor effects in human brain tumor cells
A combinatorial nanosystem with the advantages of superparamagnetic iron oxide nanoparticles (SPIO NPs) and targeting polymer carriers is expected to improve the therapeutic effects in developing multifunctional delivery systems. Here we developed an innovative tumor-specific multi-functional SPIO NPs nanoplatform containing the antitumor drug doxorubicin (DOX) and fluorescent dye rhodamine B isothiocyanate (RBITC) for theranostic analysis and anti-tumor therapy in human brain tumor U251 MG cells. The core nanocarrier SPIO NPs (γ-Fe2O3) were synthesized and decorated with chitosan (CS), subsequently followed with conjugation with tumor-specific ligand transferrin (Tf) to fabricate tumor-targeted Tf–CS/SPIO NPs. The anti-tumor drug DOX was then loaded onto Tf–CS/SPIO NPs, and transferred into U251 MG cells for assaying their biological effects. Besides, the produced Tf–CS/SPIO NPs were fluorescently labeled with RBITC for simultaneously intracellular fluorescent/magnetic resonance imaging in targeted U251 MG cells. The results showed that the fabricated Tf–CS/SPIO NPs nanocarriers demonstrated some favorable properties, including immediate responses under magnetic fields, stable behavior in different media, efficient encapsulation for drug loading, undetectable cytotoxicity, and effective intracellular visualization. Moreover, the fluorescent Tf–CS/SPIO NPs could be successfully applied for concurrent fluorescent/magnetic resonance imaging, and the finalized drug-loading Tf–CS/SPIO NPs displayed an improved cellular uptake, and thus effectively killed tumor cells through inducing a concurrence of cell apoptosis and autophagy in the treated tumor U251 cells. Therefore, the fabricated Tf–CS/SPIO NPs should be of great significance in developing multi-purpose nanocarriers for anti-tumor drug delivery and fluorescent/magnetic resonance imaging in human brain tumor treatments.
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