title: Cancer therapy and fluorescence imaging using the active release of doxorubicin from MSPs/Ni-LDH folate targeting nanoparticles.
abstract: 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.
authors.affiliation: State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science, Laboratory of Advanced Materials, Fudan University, Shanghai 200433, China.
authors.forename: Dian
authors.initials: D
authors.lastname: Li
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.forename: Jia
authors.initials: J
authors.lastname: Guo
authors.forename: Deeptangshu
authors.initials: D
authors.lastname: Chaudhary
authors.forename: Chang-Chun
authors.initials: CC
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002470:Cell Survival; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000494:pharmacology*; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D005492:Folic Acid / Q000737:chemistry; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D006878:Hydroxides / Q000737:chemistry; D054118:Nanospheres / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy; D061848:Optical Imaging / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006878:Hydroxides; D004317:Doxorubicin; C031356:hydroxide ion; D005492:Folic Acid
keywords: Core/shell nanospheres; Doxorubicin (DOX); Layered double hydroxide (LDH); Magnetic supraparticles (MSPs); Repulsive interaction