The uptake of metal–organic frameworks: a journey into the cell

Linnane, Emily; Haddad, Salame; Melle, Francesca; Mei, Zihan; Fairen‐Jimenez, David

doi:10.1039/d0cs01414a

Cited by 72 publications

(51 citation statements)

References 198 publications

(281 reference statements)

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“…This result proves that miR-124 escaped from lysosomes successfully and released into the cytoplasm, which is necessary for application of released miR-124 in NSCs. The process of lysosomal escape can be attributed to the collapse at some extent of the skeleton of Ca-MOF in an acidic environment after Ca-MOF@miR-124 nanoparticles aggregate in lysosomes, and the dissociated Ca 2+ can destroy the stability of the lysosome membrane to form holes by combining with phosphate groups enriched in the lysosome membrane. , TEM images further confirmed that Ca-MOF@miR-124 nanoparticles were endocytosed and aggregated in lysosomes in NSCs (Figure b,c). To confirm the stability of miR-124 in the acidic environment of lysosomes, retention experiments of miR-124 (8 nM) treated with Tris-HCl (pH 5.0) at 37 °C for different times (0, 12, 24, and 36 h) were performed.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, Ca-MOF@miR-124 nanoparticles were successfully internalized into NSCs and aggregated in lysosomes. After that, the acidic environment of the lysosome triggered the dissociation of hydrogen bonds between miR-124 and Ca-MOF, thus causing miR-124 to be released from the endosomal-lysosomal pathway and to access into the cellular machinery to further accelerate neuronal directed differentiation. − …”

Section: Resultsmentioning

confidence: 99%

“…We also found that Ca-MOF@miR-124 nanoparticles localized in lysosomes after being endocytosed by NSCs. Furthermore, the hydrogen bonds were rapidly broken at an acidic pH, allowing miR-124 to be released from the Ca-MOF@miR-124 nanoparticles and access the cellular machinery. − Cell experiments reveal that the Ca-MOF@miR-124 nanoparticles have high cytocompatibility and can significantly promote the neuronal directed differentiation of NSCs in vitro . This combinatorial therapeutic strategy was applied to treat a middle cerebral artery occlusion (MCAO) mouse model to further verify its ability to promote the neuronal directed differentiation of NSCs and thereby enhance the therapeutic effects of NSC therapy for ischemic stroke in vivo .…”

Section: Introductionmentioning

confidence: 99%

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Delivery of miRNAs through Metal–Organic Framework Nanoparticles for Assisting Neural Stem Cell Therapy for Ischemic Stroke

Yang

Han

et al. 2022

ACS Nano

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Stroke is the most common cause of disability globally. Neural stem cell (NSC) therapy, which can replace lost and damaged neurons, has been proposed as a potential treatment for stroke. The therapeutic efficacy of NSC therapy is hindered by the fact that only a small number of NSCs undergo neuronal differentiation. Neuron-specific miR-124, which promotes the differentiation of NSCs into mature neurons, can be combined with NSC therapy to cure ischemic stroke. However, the instability and poor internalization of miR-124 seriously hamper its broad clinical application. Herein, an innovative strategy involving delivery of miR-124 via a Ca-MOF@miR-124 nanodelivery system, which effectively prevents the degradation of miR-124 by nucleases and promotes the internalization of miR-124 by NSCs, is presented. The effect of accelerated neuronal directed differentiation of NSCs was assessed through in vitro cell experiments, and the clinical application potential of this nanodelivery system for the treatment of ischemic stroke was assessed through in vivo experiments involving the combination of NSC therapy and Ca-MOF@miR-124 nanoparticles. The results indicate that Ca-MOF@miR-124 nanoparticles can promote the differentiation of NSCs into mature neurons with electrophysiological function within 5 days. The differentiation rate of cells treated with Ca-MOF@miR-124 nanoparticles was at least 5 days faster than that of untreated cells. Moreover, Ca-MOF@miR-124 nanoparticles decreased the ischemic area to almost normal levels by day 7. The combination of Ca-MOF@miR-124 nanoparticles and NSC therapy will enhance the treatment of traumatic nerve injury and neurodegenerative diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Delivery of miRNAs through Metal–Organic Framework Nanoparticles for Assisting Neural Stem Cell Therapy for Ischemic Stroke

Yang

Han

et al. 2022

ACS Nano

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“…These findings can be used as a preliminary study for further investigations on MOFs for disrupting COVID-19 replication cycle in which other aspects of MOFs applications should be considered. Although there are some concerns regarding some specific MOFs stability in water and their ability for cell penetration, these parameters can be optimized by introduction of functional groups to the MOF structure and controlling their size 51 – 53 .…”

Section: Resultsmentioning

confidence: 99%

A computational study of metal–organic frameworks (MOFs) as potential nanostructures to combat SARS-CoV-2

Dahri

Sadeghi

Abolmaali

2022

Sci Rep

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The COVID-19 causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has a critical surface protein called spike protein (S protein), which is the target of many vaccines and drugs developments. Among non-structural proteins of SARS-CoV-2, main protease (Mpro) has drawn much attention to itself for designing antiviral drugs since it is very crucial for the virus replication in host cells. In the first part of the present study, the application of metal–organic frameworks (MOFs), one of the developing nanomaterials in the deformation and consequently inhibition of S protein binding to the receptor, angiotensin-converting enzyme 2 (ACE 2), is investigated. In this line, various S protein inhibitors were designed virtually, including ZIF, UIO, and IRMOF that their interactions with S protein and were investigated using molecular dynamics (MD) simulation. The results revealed that ZIF is the best candidate among the investigated MOFs with the least amount of energy interference with S protein. In the second part, the interaction of three-dimensional (3D) MOFs (such as ZIF, IRMOF, and HKUST) with SARS-CoV-2 Mpro was investigated. HKUST had the most potent interaction with Mpro and showed more promise in deforming this protein's secondary structure among all materials tested. Furthermore, we investigated the interaction of HKUST-OH with Mpro to determine the effect of functionalization. The findings of this study could be used in future studies to introduce bioconjugates of MOFs and biological molecules (e.g., antibody or nanobody) or to use MOFs as carriers for antiviral drug delivery.

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“…28B, panel I and II depict the in vitro release profiles of the drug. The endocytosis 237 and cytotoxicity of the VEGF-responsive DOX-loaded NMOFs gated with the ( 62 )/( 63 ) or ( 62 )/( 64 ) locks toward MDA-MB-231 breast cancer cells and normal MCF-10A epithelial breast cells was examined by subjecting the respective locked NMOFs to the respective cells, Fig. 28C.…”

Section: G-quadruplex-responsive Carriers For Therapeutic Applicationsmentioning

confidence: 99%

Switchable and dynamic G-quadruplexes and their applications

2022

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The uptake of metal–organic frameworks: a journey into the cell

Abstract: This review critically evaluates the recent advancements in the understanding of endocytosis of nano-sized metal–organic frameworks and the importance of biological context in aiding MOF rational design and synthesis for drug delivery applications.

Cited by 72 publications

References 198 publications

Delivery of miRNAs through Metal–Organic Framework Nanoparticles for Assisting Neural Stem Cell Therapy for Ischemic Stroke

Delivery of miRNAs through Metal–Organic Framework Nanoparticles for Assisting Neural Stem Cell Therapy for Ischemic Stroke

A computational study of metal–organic frameworks (MOFs) as potential nanostructures to combat SARS-CoV-2

Switchable and dynamic G-quadruplexes and their applications

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