TY - JOUR
T1 - Biocompatibility characteristics of the metal organic framework ZIF-8 for therapeutical applications
AU - Hoop, Marcus
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
PY - 2018/6/1
Y1 - 2018/6/1
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.
KW - Biocompatibility
KW - Biomedical applications
KW - Metal organic framework
KW - Zeolitic imidazolate framework
KW - ZIF-8
KW - Zn
UR - http://www.scopus.com/inward/record.url?scp=85041567199&partnerID=8YFLogxK
U2 - 10.1016/j.apmt.2017.12.014
DO - 10.1016/j.apmt.2017.12.014
M3 - Article
AN - SCOPUS:85041567199
SN - 2352-9407
VL - 11
SP - 13
EP - 21
JO - Applied Materials Today
JF - Applied Materials Today
ER -