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Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles

Dian Li,Yu-Ting Zhang,Meng Yu,Jia Guo,Deeptangshu Chaudhary,Chang-Chun Wang

Hierarchical structured nanomaterials with diverse functionality, such as magnetic susceptibility , stimuli-responsiveness, environmental sensing and biocompatibility, are highly sought after for biomedicine and biodetection alike. In this study, we designed and fabricated a new kind of multifunctional core/shell nanospheres as biodegradable targeted drug carriers, the controlled drug release progress and therapeutic effect were monitored in-situ by the fluorescent state of the cells. Firstly, the core/shell nanospheres with biodegradability were synthesized using magnetic supraparticles (MSPs) as core and the layered double hydroxide (LDH) as shell via a hydrothermal route, the reaction parameters were well investigated to obtain the desired structure of the LDH shell. The anti-cancer drug doxorubicin was modified with carboxyl group (DOX-COOH) and loaded in the shell of MSPs/LDH nanospheres via an anion-exchange intercalation. To endow the nanospheres with tumor-targeting capability, IDA (iminodiacetic acid)-modified folate was successfully immobilized onto the surface of LDH shell using chelating interaction. These nanospheres behaved as multifunctional carriers for targeted delivery of anti-cancer drug, doxorubicin (DOX), within Hela cells and thus, these nano-drugs exhibited clear cytotoxicity and inhibition toward Hela cells as compared to normal cell-lines of HEK 293T cells. Interestingly, after the internalization of these nano-drugs, there was a sharp contrast in illumination between the tumorous Hela cells and the normal HEK 293T cells, the acidic cytoplasm of Hela cell stimulated DOX-COOH in LDH shell quickly degraded into positive-charged DOX, and then rapidly escaped from the positive-charged intercalation of LDH shell by strong repulsive interaction, the released DOX rapidly lit up the whole tumor cells in a short time, but only very weak light was found in HEK 293T cells.