ZIF-8 degrades in cell media, serum, and some—but not all—common laboratory buffers

Abstract

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; however, cargo inside the ZIF-8 does not appear to leak out, in most of these buffers, even when the ZIF-8 itself is displaced by phosphates. On the other hand, 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 in vivo.

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy

“…57 Luzuriaga et al studied the stability of ZIF-8 single crystals in common laboratory buffers (phosphate buffer and bicarbonate buffer), cell culture media, serum, and whole cell culture media, which provides a reference for the choice of buffer for sustained release of drugs in vitro and in vivo. 58 The size of ZIF-8 particles will also affect the drug release process. Research by Velásquez-Hernández et al showed that the degradation rate of ZIF-8 particles in phosphate buffered saline (PBS) is related to their size.…”

Continuous‐Flow Synthesis of ZIF‐8 Biocomposites with Tunable Particle Size

“…The most extensively investigated topology is sodalite ( sod ) as it has been shown to afford crystalline microporous materials that can protect encapsulated proteins from inhospitable environments . Furthermore, the sod ZIF‐8 coating can be degraded under mild conditions (mild acidic conditions, phosphate ions or chelating agents) allowing for triggered release of the encapsulated biomolecule with retention of its native activity …”

Fabricating Bioactive 3D Metal–Organic Framework Devices

“…We tested our prototype device using Tris buffer (100 m m , pH 8) because ZIF‐8 in its unfunctionalized form, has good stability in neutral and basic pH solutions but it is structurally unstable in acidic conditions. [ 29 ] However, the acid stability of ZIFs can be reinforced by modification using functional groups such as carboxylates and phosphates (lower pKa than imidazolate ligand). [ 30 ] Alternative MOFs such as NH 2 ‐MIL‐53 and Mg‐MOF‐74 have also been demonstrated for biomimetic mineralization of enzymes.…”