Ligand exchange triggered controlled-release targeted drug delivery system based on core-shell superparamagnetic mesoporous microspheres capped with nanoparticles

摘要

We report a new controlled-release targeted drug delivery system based on core-shell structured silica mesoporous microspheres capped with superparamagnetic iron oxide nanoparticles. A ligand exchange strategy was developed to release guest molecules loaded in the mesopores. The system possesses a stimuli-responsive release property for the entrapped guest molecules, which is important for the delivery of toxic anticancer drugs in chemotherapy. A variety of stimulating agents, such as EDTA and sodium citrate, have been used to release the entrapped guest molecules, relying on the new ligand exchange triggered release mechanism. The release rate of guest molecules can be controlled by using different trigger-agents. The drug delivery system possesses high saturation magnetization (~58 emu g~(-1)) and superparamagnetic character, and thus can be easily enriched by a permanent magnet and re-dispersed in PBS solutions, which greatly facilitates its manipulation in practical applications. Cytotoxicity analyses of the drug delivery system based on human gastric cancer SGC-7901 and rat pheochromocytoma PC12 cells show low cytotoxicity and good biocompatibility. The uptake properties of the system by SGC-7901 and human cervical carcinoma HeLa cells demonstrate their great potential for applications in drug delivery. Furthermore, in vitro experiments show that cancer cells can be effectively killed by anticancer drug (paclitaxel) released from the system, further indicating the promise of the controlled-release drug delivery system in cancer treatment.