Abstract
A charge reversible, magnetic-targeted, and pH-responsive nano therapy system assembled from citraconic-modified dextran (Dex–COOH), glycine-stabilized superparamagnetic iron oxide nanoparticles (SPION–NH2), and doxorubicin (DOX) through electrostatic interaction was designed for delivering therapeutics to tumor cells. Dex–COOH was first synthesized to build the pH-sensitive citraconic amide bond and further render charge reversal upon the cleavage of the linkage. The SPION–NH2 anchored in the nanocarrier endows the carrier with magnetic migration. The vibrating sample magnetometer analysis exhibits the superparamagnetic behavior, and the magnetic saturation value is estimated to be 39.6 emu (g Fe)−1. The change of size and the reversal of zeta potential from negative to positive in acidic environment confirmed these expected responsibilities. The DOX-loaded nanocarriers contain DOX up to 13.0 wt%. An in vitro release profile demonstrated an efficient DOX release of 80 % at pH 5.0 while of 27 % at pH 6.8 and 13 % at pH 7.4, suggesting a pH-induced release mechanism. Microscopic images of Prussian blue staining, quantification of cellular iron and protein concentration displayed apparent iron uptake by HeLa cells. Confocal laser scanning microscopy observations revealed that the nanocarriers could efficiently deliver and release DOX into the nuclei of HeLa cells. MTT assays testified that DOX-loaded nanocarrier exhibited high anti-tumor activity with IC50 of 0.7 μg mL−1, while plain nanocarriers were practically non-toxic. This drug delivery system has shown the ability to improve the chemotherapeutic efficacy and to reduce the side effects, indicating great potential for delivery of drugs to the targeted sites in patients.
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