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

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 due to its remarkable loading capacity, stability in physiological environments, and pH triggered controlled drug release. Using 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 towards six different cell lines representing various body parts (kidney, skin, breast, blood, bones, and connective tissue). Our results suggested that ZIF-8 has no significant cytotoxicity up to a threshold value of 30 µg/mL. Above 30 µg/mL the cytotoxicity is shown to result from the effect of released Zinc ions (Zn 2+) on the mitochondrial ROS production, causing cell cycle arrest in the G2/M phase due to irreversible DNA damage, and ultimately initiating cellular apoptosis pathways. Due to this insight, we then encapsulated the hormone insulin into ZIF-8 and compared its drug delivery capabilities to the aforementioned cytotoxicity values. Our results suggest that ZIF-8 is suitable for therapeutic applications and furthermore, establish a clear understanding of the interaction of ZIF-8 and its constituents with various cell lines including, and highlight the important biocompatibility factors that must be considered for future in vivo testing.

Phase dependent encapsulation and release profile of ZIF-based biocomposites

“…viruses and living cells) from conditions that typically lead to loss of their activity and also act as a vector for in vitro and in vivo delivery. 11,12,15,[19][20][21][22][23] With respect to drug delivery applications, the biomimetic mineralization approach yields high encapsulation efficiencies (EE%) for biomacromolecules, typically ranging from 80% to 100%. 11,18,21 In general, high EE% values are relevant to drug delivery applications as the therapeutic is the valuable component of the composite.…”

Omniphobic ZIF‐8@Hydrogel Membrane by Microfluidic‐Emulsion‐Templating Method for Wound Healing

“…To gain insights into the bactericidal mechanism of the omniphobic hydrogel membrane, we characterized the release kinetics of zinc ions (Zn 2+ ) originating from ZIF‐8 nanoparticles. Zn 2+ is mainly responsible for killing E. coli for that it can destabilize the microbial membrane; meanwhile, the good compatibility of imidazolate linkers also assists Zn 2+ in the bactericidal process 40,41. During the wound healing, the crystalline structure of ZIF‐8 collapses slowly and Zn 2+ ions release sustainably.…”

“…It is practically important to find out the suitable amount of ZIF‐8 nanoparticles in the omniphobic wound dressings, since a fast release of zinc ions could be cytotoxic to cells 41. To validate this, we test the cytotoxicity of omniphobic ZIF‐8@PVA hydrogel membranes with different ZIF‐8 concentrations, by the extract solution method and MTT assay, as shown in Figure a,c.…”

Metal-Organic Framework Encapsulated Whole-Cell Vaccines Enhance Humoral Immunity against Bacterial Infection

“…[19][20][21][22][23][24][25][26][27] We and others have described a specific type of MOF called ZIF-8, 28, 29 composed exclusively of zinc metals interconnected by methylimidazole ligands, that crystallize "biomimetically" on a variety of biomacromolecules including soluble proteins, polysaccharides, viruses, and whole cells. [30][31][32][33][34][35][36] For this study, we used CFT073, a model urosepsis strain of UPEC frequently employed in the development of new vaccines. 37 Gram-negative E. coli has an outer membrane containing embedded polysaccharides and proteins, [38][39][40] which support ZIF-8 growth ( Figure 1C).…”