Degradation Mechanism of Porous Metal-Organic Frameworks by In Situ Atomic Force Microscopy

Abstract

In recent years, Metal-Organic Frameworks (MOFs) have attracted a growing interest for biomedical applications. The design of MOFs should take into consideration the subtle balance between stability and biodegradability. However, only few studies have focused on the MOFs’ stability in physiological media and their degradation mechanism. Here, we investigate the degradation of mesoporous iron (III) carboxylate MOFs, which are among the most employed MOFs for drug delivery, by a set of complementary methods. In situ AFM allowed monitoring with nanoscale resolution the morphological, dimensional, and mechanical properties of a series of MOFs in phosphate buffer saline and in real time. Depending on the synthetic route, the external surface presented either well-defined crystalline planes or initial defects, which influenced the degradation mechanism of the particles. Moreover, MOF stability was investigated under different pH conditions, from acidic to neutral. Interestingly, despite pronounced erosion, especially at neutral pH, the dimensions of the crystals were unchanged. It was revealed that the external surfaces of MOF crystals rapidly respond to in situ changes of the composition of the media they are in contact with. These observations are of a crucial importance for the design of nanosized MOFs for drug delivery applications.

MIL-100(Fe) Sub-Micrometric Capsules as a Dual Drug Delivery System

“…All characteristics were, on the whole, in agreement with previous results, including a BET surface area of 1300 m 2 g −1 . The nanoparticles exhibited a mean diameter of 80 ± 30 nm, as determined by dynamic light scattering (DLS) ( Figure S1 ), 66 ± 12 nm, as determined by transmission electron microscopy (TEM) ( Figure 1 D) associated with a ζ potential (deionized water) of −24 ± 0.6 mV, consistent with the literature [ 16 , 17 ]. Furthermore, the nitrogen physisorption of MIL-100(Fe) NPs exhibited BET surface area and BJH pore size distribution according to what was previously reported in the literature, as shown in Figure S2 .…”

“…At pH 5.0, the kinetics of release was overall slower than the one observed at pH 7.4. Such a difference in release profiles could be due to the greater stability of the constitutive MOF (and, thus, MOF capsule) in the acidic medium, releasing only a small amount of collagenase present inside the MIL-100 capsule and more pronounced degradation in a neutral PBS, which, consequently, led to a higher collagenase release [ 17 ]. This longer sustained release of the enzyme, which fits well with the one of MTX under the same conditions, can be explained by its localization within the core of the capsule.…”

“…Among all the MOFs nanocarriers reported to date, the mesoporous iron trimesate MIL-100(Fe) (MIL stands for Materials from Institute Lavoisier) is one of the most promising MOFs in biomedicine due to its very high porosity, open metal sites as well as its lack of toxicity due to its bio-friendly composition and biodegradable character [ 14 , 15 ]. Previous studies indicated that MIL-100(Fe) NPs are stable in aqueous and ethanolic solution but degrade progressively in simulated biological media, particularly at pH 7.4 [ 16 , 17 ]. However, we hypothesize here that aggregating MOF NPs to form a porous capsule by spray-drying can interfere with the rate of degradation of the nanoparticles, and, thus, the release of the drugs, while enabling the enzyme to be incorporated within the additional mesopores from the capsule (interparticular and internal cavities).…”

Growth of Fe‐BDC Metal‐Organic Frameworks onto Functionalized Si (111) Surfaces

“…A lack of AFM tip resolution preventing the pore observation cannot be discarded however. Similar stair‐case structure was reported recently in the case of MIL‐100(Fe) single crystal deposited onto ITO thin layer on glass [30] . In this case also flat (111) terraces separated by ∼4.5 nm high steps corresponding to the d 111 reticular distance of the cubic MIL‐100(Fe) structure were observed by AFM.…”

Porous Metal–Organic Framework Nanoparticles

“…Understanding how the structural defects of the particles affect their degradation rate is of pivotal importance to pave the way for their clinical use as delivery systems in biological media. One of the articles within this Special Issue describes the latest findings on this issue through the use of atomic force microscopy [ 2 ].…”