Study Of Multifunctional Magnetic Nanocarrier For Anticancer Drug Controlled Release

In recent years,cancer has become an unnegligible obstruct in the development of human beings.With the rapid development of medical biomaterials,the biodegradable polymers which can be easily modified are getting more and more attraction,especially in the application of anticancer drug delivery system.Various kinds of stimuli drug carriers were designed based on the slight differences between the microenvironment of tumor and normal tissue to achieve good cancer therapeutic effect with low toxicity.In this paper,how to minimize the leakage of anti-cancer drug during the transportation to aviod systemic side effects was the main focus of our attention.At first,a reduction-triggered superparamagnetic nanogel was designed by the electrostatic interaction between the aminated superparamagnetic iron oxide nanoparticles and sodium alginate anchored doxorubicin to enhance targeting release but minimize leakage of drug in the transportation pathway.All the chemical modifications were proved by FTIR,1H-NMR and spectral analysis.The nanogel was estimated with a size of 122±15 nm,a polydispersity index of 0.178,a surface charge of around-36.0±0.9 m V,a DOX loading efficiency of 7.2 wt%,and a saturation magnetization of 40.0 emu/g Fe.In vitro release profiles showed a significantly high accumulative release at p H 5.5/10 m M Glutathione(GSH)but pretty low release at p H 7.4 or p H 5.5 without GSH,exhibiting apparent reduction responsiveness.In vitro cytotoxicity tests clearly illustrated the effective selectivity of nanogels.Prussian blue staining and quantification of cellular iron results revealed apparent iron uptake by He La cells.Confocal laser scanning microscopy observation demonstrated that DOX was efficiently internalized into He La cells,released into the cytoplasm,and then principally entered the nuclei.In vivo investigation exhibited that nanogel treatment induced obvious shrinkage in tumor volume but a stable growth in body weight and a healthy appearance.Hematoxylin-eosin(H&E)staining indicated remarkable necrosis in the tumor area and histological examination revealed lower toxicity in vital organs.Based on above,another delivery system showing synergism effect on cancer therapy was achieved through the additional introduction of surface decoration-selenium nanoparticle.The successful selenium nanoparticle adding was proved by EDX,ICP-MS and TEM.The nanogel was estimated with a size of 166.4±12.7 nm,a polydispersity index of 0.25,a surface charge of-23.6±1.2 m V,a DOX loading efficiency of 6.5 wt%,and a saturation magnetization of 37.2 emu/g Fe.In vitro release profiles exhibited apparent reduction responsiveness.Compared with the first carrier we prepared,significant cytotoxicity improvement was observed in cells experiment due to the synergism effect both of DOX and selenium nanoparticle.Meanwhile,permanent magnetic field attraction was applied for enhancing the nanogels accumulation at targeted site and accelerating the uptake rate in a short time to achieve increased inhibition behavior of cancer cell growth.In all above,to decrease the adverse systemic effect,firstly,we used chemical conjugation way to carry the anticancer drug for minimizing leakage in delivery pathway.And then,we developed a synergism system by the combination of anticancer drug and inorganic selenium nanoparticle toward to minimize drug dosage.We believe that these two drug carriers provide the application value for the future study.