Microcurvature Controllable Metal–Organic Framework Nanoagents Capable of Ice-Lattice Matching for Cellular Cryopreservation

Abstract

Ice-binding proteins (IBPs) produced by psychrophilic organisms to adapt for the survival of psychrophiles in subzero conditions have received illustrious interest as a cryopreservation agent required for cells and tissues to completely recover after freezing/thawing. Depressing water-freezing point and avoiding ice-crystal growth affect their activities which are closely related to the presence of ice crystal well-matched binding moiety. The interaction of IBPs with ice and water is critical in enhancing their freeze avoidance against cell or tissue damage. Metal–organic frameworks (MOFs) with a controllable lattice at the molecular level and a size at the nanometer scale can offer periodically ordered ice-binding sites by modifying organic linkers and controlling microcurvature at the ice surface. Herein, zirconium (Zr)-based MOF-801 nanoparticles (NPs) with good biocompatibility were used as a cryoprotectant that is well dispersed and colloidal-stable in an aqueous solution. The MOF NP size was precisely controlled, and 10, 35, 100, and 250 nm NPs were prepared. The specific IBPs-mimicking pendants (valine and threonine) were simply introduced into the MOF NP-surface through the acrylate-based functionalization to endow with hydrophilic and hydrophobic dualities. When small-sized MOF-801 NPs were attached to ice, they confined ice growth in high curvature between the adsorption sites because of the decreased radius of the convex area of the growth region, leading to highly enhanced ice recrystallization inhibition (IRI). Surface-functionalized MOF NPs could increase the number of anchored clathrate water molecules with hydrophilic/hydrophobic balance of the ice-binding moiety, effectively inhibiting ice growth. The MOF-801 NPs were biocompatible with various cell lines regardless of concentration or NP surface-functionalization, whereas the smaller-sized surface-functionalized NPs showed a good cell recovery rate after freezing/thawing by induction of IRI. This study provides a strategy for the fabrication of low-cost, high-volume antifreeze nanoagents that can extend useful applications to organ transplantation, cord blood storage, and vaccines/drugs.

Dimensional Reduction of Metal–Organic Frameworks for Enhanced Cryopreservation of Red Blood Cells

“…The average sizes of the MOLs with different organic ligands were all in the sub‐micrometer range and would be comparable with the size of 2D Hf‐TATB MOLs. Despite the exact size of nanostructures would alter their IRI activity and cryopreservation efficiency, the size differences at the submicrometer ranges may show little effect on these properties for non‐permeable CPAs [9a,b, 14] . Therefore, the influence of their size differences were ignored temporarily in current work.…”

“…[2b] So far, the existing spectrum of MOFs with known structures is already up to 100 000, [13] which opens a wide opportunity for structure design. [14] However, from the morphology point of view, 3D MOF NPs as CPA have their limitations: 1) Not ideal contact pattern -hard 3D MOFs cannot conform to the ice surface and have limited extents of hydrogen bonding interactions with ice; 2) Low ordered-structure utilization efficiency-when 3D MOF NPs are used for cryopreservation, only a few exposed crystal surfaces can interact with ice crystal planes, however, the internal ordered structures are not accessible and usable. Based on the above assumption, we propose that through a dimensional reduction approach where 3D MOF NPs are gradually reduced to 2D ultra-thin, flexible metal-organic layers (MOLs), it may be a simple but effective strategy to enhance cryopreservation efficiency.…”

“…Hydrogen bonding interactions at interfaces play a key role in ice modulation [2b] . So far, the existing spectrum of MOFs with known structures is already up to 100 000, [13] which opens a wide opportunity for structure design [14] . However, from the morphology point of view, 3D MOF NPs as CPA have their limitations: 1) Not ideal contact pattern—hard 3D MOFs cannot conform to the ice surface and have limited extents of hydrogen bonding interactions with ice; 2) Low ordered‐structure utilization efficiency—when 3D MOF NPs are used for cryopreservation, only a few exposed crystal surfaces can interact with ice crystal planes, however, the internal ordered structures are not accessible and usable.…”

De novo design of a nanoregulator for the dynamic restoration of ovarian tissue in cryopreservation and transplantation

“…In 2023, Jeon’s team harnessed MOF NPs as cryoprotectants, capitalizing on their ability to modify organic linkers and control ice surface micro-curvature [ 146 ]. This strategic manipulation facilitated the creation of cyclically ordered ice-binding sites, effectively reducing ice crystal formation and advancing the prospects for cellular cryopreservation.…”

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Fig. 6 Mechanism of different types of zirconium-based metal and organic frame-based nanoregulators (MOF NPs) inhibiting ice crystal growth [ 145 , 146 ]. A Schematic illustration of the solvothermal synthesis of MOF-801 NPs.

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