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Optimized metal-organic-framework nanospheres for drug delivery: evaluation of small-molecule encapsulation.

Abstract
We have developed a general synthetic route to encapsulate small molecules in monodisperse zeolitic imid-azolate framework-8 (ZIF-8) nanospheres for drug delivery. Electron microscopy, powder X-ray diffraction, and elemental analysis show that the small-molecule-encapsulated ZIF-8 nanospheres are uniform 70 nm particles with single-crystalline structure. Several small molecules, including fluorescein and the anticancer drug camptothecin, were encapsulated inside of the ZIF-8 framework. Evaluation of fluorescein-encapsulated ZIF-8 nanospheres in the MCF-7 breast cancer cell line demonstrated cell internalization and minimal cytotoxicity. The 70 nm particle size facilitates cellular uptake, and the pH-responsive dissociation of the ZIF-8 framework likely results in endosomal release of the small-molecule cargo, thereby rendering the ZIF-8 scaffold an ideal drug delivery vehicle. To confirm this, we demonstrate that camptothecin encapsulated ZIF-8 particles show enhanced cell death, indicative of internalization and intracellular release of the drug. To demonstrate the versatility of this ZIF-8 system, iron oxide nanoparticles were also encapsulated into the ZIF-8 nanospheres, thereby endowing magnetic features to these nanospheres.
AuthorsJia Zhuang, Chun-Hong Kuo, Lien-Yang Chou, De-Yu Liu, Eranthie Weerapana, Chia-Kuang Tsung
JournalACS nano (ACS Nano) Vol. 8 Issue 3 Pg. 2812-9 (Mar 25 2014) ISSN: 1936-086X [Electronic] United States
PMID24506773 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Capsules
  • Cetrimonium Compounds
  • Drug Carriers
  • Imidazoles
  • Organometallic Compounds
  • Cetrimonium
Topics
  • Capsules
  • Cell Survival (drug effects)
  • Cetrimonium
  • Cetrimonium Compounds (chemistry)
  • Drug Carriers (chemistry, toxicity)
  • Humans
  • Imidazoles (chemistry)
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Conformation
  • Nanospheres (chemistry, toxicity)
  • Organometallic Compounds (chemistry, toxicity)
  • Particle Size

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