ZIF-8 Degrades in Cell Media, Serum, and Some—But Not All—Common Laboratory Buffers

Abstract

<p>The emergence of drug delivery using water stable metal-organic frameworks has elicited a lot of interest in their biocompatibility. However, few studies have been conducted on their stability in common buffers, cell media, and blood proteins. For these studies, single crystal ZIF-8 approximately 1 um in diameter were synthesized, incubated with common laboratory buffers, cell media, and serum, and then characterized by PXRD, IR, DLS, and SEM. Time-resolved SEM and PXRD demonstrate that buffers containing phosphate and bicarbonate alter the appearance and composition of ZIF-8. Further, blood proteins in serum dissolve ZIF-8, causing trapped biomolecules to escape. The study presented here suggests that ZIF-8 can undergo dramatic surface chemistry changes that may affect the interpretation of cellular uptake and cargo release data. On the other hand, it provides a rational explanation as to how ZIF-8 neatly dissolves <i>in vivo</i>. </p>

Phase dependent encapsulation and release profile of ZIF-based biocomposites

“…phosphate-buffered saline, PBS). 18,24,25 ZIF-8 is a crystalline microporous material with sodalite (sod) topology that is synthesized by mixing aqueous solutions of HmIM and Zn 2+ . [26][27][28] However, by varying the synthetic conditions, other topologies can be obtained (e.g.…”

Degradation of ZIF-8 in phosphate buffered saline media

“…10 Another important property that needs to be considered for the drug release performance of MOFs is how the material degrades under physiological conditions. [30][31][32][33] Ruyra et al demonstrated that several nanoMOFs (e.g. UiO-67, ZIF-7, HKUST-1) become amorphous or decompose releasing cations when exposed to the cell culture medium (Dulbecco's modified Eagle's medium).…”

“…9 In another study, Luzuriaga et al showed that ZIF-8 can degrade in several buffer solutions suggesting that this aspect should be taken into account for biotechnological applications. 33 However, the mechanism of degradation of ZIF-8 particles in PBS has not been fully elucidated and the related kinetics of decomposition remain unknown.…”

Identifying Differing Intracellular Cargo Release Mechanisms by Monitoring In Vitro Drug Delivery from MOFs in Real Time

“…In this study, we probe Dox (in the form of doxorubicin hydrochloride) loading and release using UiO-66, which has been studied intensely for drug delivery, 59 as a small-pore MOF (ZIF-8 has been shown to have poor stability to pH < 7 60 and in certain biological buffers 61 , 62 ) and MIL-101(Cr), in which BDC linkers connect trimeric Cr 3 O(RCO 2 ) 6 (H 2 O) 2 X (X = a monoanion) SBUs into the mtn topology with pore apertures of 12.0, 14.7, and 16.0 Å in diameter, 63 as a large-pore MOF. There are a small number of studies into Dox uptake and delivery by MIL-101(Fe) and derivatives, 34 , 64 , 65 , 66 one of which is clearly indicative of pore loading, 67 but none into MIL-101(Cr).…”