Structural Optimization Of Magnetic Nanocarriers For Controlled Drug Release

In recent years, the traditional medicines for cancer treatment revealed many shortcomings: hydrophobicity of cancer drug, side effects on normal tissues and low utilization rate. Among the many enviroumental responsive materials, redox responsive, pH responsive and magnetic responsive materials were especially favoured by scholars. The experimental results showed that dextran/magenatic iron oxide nanoparticles possessed superior acid sensitivity, which is expected to be applied to enhance targeted anticancer drug delivery efficiency by simultaneously promoting drug accumulation at the tumor cells via EPR effect and facilitating the cell internalization and intracellular drug release.At first, 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 He La cells. Confocal laser scanning microscopy(CLSM) 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 ?g 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.Then, a novel magnetic drug-targeting carrier consisting of magnetic nanoparticles encapsulated with a smart polymer with characteristics of controlled drug release is described. The amino-modified dextran whose lateral chain contains reduction-sensitive disulfide linkages groups were synthesized, and the reduction-sensitive magnetic nanoparticles were prepared with citrate-modified iron oxide nanoparticles by electrostatic interactions. Finally, carboxylic dextran derivates whose lateral chain contains acid-sensitive groups were synthesized, and followed by composite with the reduction-sensitive magnetic nanoparticles via electrostatic interactions. The morphology of nanoparticles were observed by transmission electron microscopy(TEM)and the particle size of them was determined by Malvern laser diffraction analyzer. The cytotoxicity assay demonstrated that the nanoparticles were non-toxic and DOX remained biologically active after incorporation into the nanoparticles.This intelligent drug delivery system has showed the ability to to enhance targeted anticancer drug delivery efficiency.