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

Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

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.

Originalspracheenglisch
Seiten (von - bis)13-21
Seitenumfang9
FachzeitschriftApplied Materials Today
Jahrgang11
DOIs
PublikationsstatusVeröffentlicht - 1 Jun 2018

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Biocompatibility
Zinc
Metals
Cytotoxicity
Cells
Drug delivery
Tissue
Insulin
Hormones
Cell death
Skin
Bone
DNA
Blood
Ions
Apoptosis
Crystalline materials
Testing

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    ASJC Scopus subject areas

    • !!Materials Science(all)

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    Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications. / Hoop, Marcus; Walde, Claudio F.; Riccò, Raffaele; Mushtaq, Fajer; Terzopoulou, Anastasia; Chen, Xiang Zhong; deMello, Andrew J.; Doonan, Christian J.; Falcaro, Paolo; Nelson, Bradley J.; Puigmartí-Luis, Josep; Pané, Salvador.

    in: Applied Materials Today, Jahrgang 11, 01.06.2018, S. 13-21.

    Publikation: Beitrag in einer FachzeitschriftArtikelForschungBegutachtung

    Hoop, M, Walde, CF, Riccò, R, Mushtaq, F, Terzopoulou, A, Chen, XZ, deMello, AJ, Doonan, CJ, Falcaro, P, Nelson, BJ, Puigmartí-Luis, J & Pané, S 2018, 'Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications' Applied Materials Today, Jg. 11, S. 13-21. https://doi.org/10.1016/j.apmt.2017.12.014
    Hoop, Marcus ; Walde, Claudio F. ; Riccò, Raffaele ; Mushtaq, Fajer ; Terzopoulou, Anastasia ; Chen, Xiang Zhong ; deMello, Andrew J. ; Doonan, Christian J. ; Falcaro, Paolo ; Nelson, Bradley J. ; Puigmartí-Luis, Josep ; Pané, Salvador. / Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications. in: Applied Materials Today. 2018 ; Jahrgang 11. S. 13-21.
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    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.",
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    AU - Walde, Claudio F.

    AU - Riccò, Raffaele

    AU - Mushtaq, Fajer

    AU - Terzopoulou, Anastasia

    AU - Chen, Xiang Zhong

    AU - deMello, Andrew J.

    AU - Doonan, Christian J.

    AU - Falcaro, Paolo

    AU - Nelson, Bradley J.

    AU - Puigmartí-Luis, Josep

    AU - Pané, Salvador

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    N2 - 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.

    AB - 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.

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    KW - Zeolitic imidazolate framework

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