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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.
AuthorsDian Li, Yu-Ting Zhang, Meng Yu, Jia Guo, Deeptangshu Chaudhary, Chang-Chun Wang
JournalBiomaterials (Biomaterials) Vol. 34 Issue 32 Pg. 7913-22 (Oct 2013) ISSN: 1878-5905 [Electronic] Netherlands
PMID23886730 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Copyright© 2013 Elsevier Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Hydroxides
  • Doxorubicin
  • hydroxide ion
  • Folic Acid
Topics
  • Antineoplastic Agents (pharmacology)
  • Cell Survival
  • Delayed-Action Preparations
  • Doxorubicin (pharmacology)
  • Drug Carriers (chemistry, pharmacology)
  • Folic Acid (chemistry)
  • HEK293 Cells
  • HeLa Cells
  • Humans
  • Hydroxides (chemistry)
  • Nanospheres (chemistry)
  • Neoplasms (drug therapy)
  • Optical Imaging (methods)

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