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

Jia Zhuang, Chun Hong Kuo, Lien Yang Chou, De Yu Liu, Eranthie Weerapana*, Chia Kuang Tsung

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

660 Scopus citations


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.

Original languageEnglish
Pages (from-to)2812-2819
Number of pages8
JournalACS Nano
Issue number3
StatePublished - 25 Mar 2014


  • cellular uptake
  • drug delivery
  • nanoparticles
  • ZIF-8


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