Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications

Marcus Hoop*, Claudio F. Walde, Raffaele Riccò, Fajer Mushtaq, Anastasia Terzopoulou, Xiang Zhong Chen, Andrew J. deMello, Christian J. Doonan, Paolo Falcaro, Bradley J. Nelson, Josep Puigmartí-Luis, Salvador Pané

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Metal–organic frameworks (MOFs) are a class of crystalline materials constructed from organic linkers and inorganic nodes. MOFs typically possess ultra-high surface areas and pore volumes; thus, they are ideal candidates for biomedical applications. Zinc Imidazolate Framework 8 (ZIF-8) has been widely established in the literature as a potential candidate for on-demand drug delivery applications. Indeed, ZIF-8 has a remarkable loading capacity, stability in physiological environments, and tunable drug release properties. However, the use of ZIF-8 for in vivo applications requires a clear understanding of the interaction of ZIF-8 with biological tissue. In this work, we investigated the biocompatibility of ZIF-8 toward six different cell lines representing various body parts (kidney, skin, breast, blood, bones, and connective tissue). Our results suggest that ZIF-8 has no significant cytotoxicity up to a threshold value of 30 μg mL−1. Above 30 μg mL−1, the cytotoxicity is shown to result from the influence of released Zinc ions (Zn2+) on the mitochondrial ROS production. This adverse effect is responsible for cell cycle arrest in the G2/M phase due to irreversible DNA damage, ultimately initiating cellular apoptosis pathways. Due to this insight, we encapsulated a hormone, insulin, into ZIF-8 particles and then compared its drug delivery capabilities to the aforementioned cytotoxicity values. Our results suggest that ZIF-8 is suitable for therapeutic applications. Furthermore, this study establishes a clear understanding of the interaction of ZIF-8 and its constituents with various cell lines and highlights the important biocompatibility factors that must be considered for future in vivo testing.

Original languageEnglish
Pages (from-to)13-21
Number of pages9
JournalApplied Materials Today
Volume11
DOIs
Publication statusPublished - 1 Jun 2018

Keywords

  • Biocompatibility
  • Biomedical applications
  • Metal organic framework
  • Zeolitic imidazolate framework
  • ZIF-8
  • Zn

ASJC Scopus subject areas

  • Materials Science(all)

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