The construction of efficient enzyme mimetics for the hydrolysis of peptide bonds in proteins is challenging due to the high stability of peptide bonds and the importance of proteases in biology and industry. Metal-organic frameworks (MOFs) consisting of infinite crystalline lattices with metal clusters and organic linkers may provide opportunities for protease mimic which has remained unknown. Herein, we report that Cu2(C9H3O6)4/3 MOF (which is well known as HKUST-1 and denoted as Cu-MOF here), possesses an intrinsic enzyme mimicking activity similar to that found in natural trypsin to bovine serum albumin (BSA) and casein. The Michaelis constant (Km) of Cu-MOF is about 26,000-fold smaller than that of free trypsin indicating a much higher affinity of BSA for Cu-MOF surface. Cu-MOF also exhibited significantly higher catalytic efficiency than homogeneous artificial metalloprotease Cu(II) complexes and could be reused for ten times without losing in its activity. Moreover, Cu-MOF was successfully used to simulate trypsinization in cell culture since it dissociated cells in culture even without EDTA.
Though metal-organic frameworks (MOFs) have inspired potential applications in biomedicine, cytotoxicity studies of MOFs have been relatively rare. Here we demonstrate for the first time that an easily available MOF, Fe-MIL-101, possesses intrinsic activity against human SKOV3 ovarian cancer cells and suppress the proliferation of SKOV3 cells (IC50 = 23.6 μg mL−1) and normal mouse embryonic fibroblasts (BABL-3T3, IC50 = 78.3 μg mL−1) cells. It was more effective against SKOV3 cells than typical anticancer drugs such as artesunate (ART, IC50 = 96.9 μg mL−1) and oxaliplatin (OXA, IC50 = 64.4 μg mL−1), but had less effect on normal BABL-3T3 cells compared with ART (IC50 = 36.6 μg mL−1) and OXA (IC50 = 13.8 μg mL−1). Fe-MIL-101 induced apoptosis of human umbilical vein endothelial cells (HUVECs) via G0/G1 cell cycle arrest and decreased the mitochondrial membrane potential in HUVECs and induced apoptosis. Furthermore, Fe-MIL-101 exhibited stronger antiangiogenic effects in HUVEC cells than antiangiogenic inhibitor (SU5416) via downregulation the expression of MMP-2/9. Our results reveal a new role of Fe-MIL-101 as a novel, non-toxic anti-angiogenic agent that restricted ovarian tumour growth. These findings could open a new avenue of using MOFs as potential therapeutics in angiogenesis-dependent diseases, including ovarian cancer.
Solar-driven photocatalytic H2O2 production with water and O2 is an environmentally friendly process for producing H2O2, an important chemical. Compared with traditional photocatalysts, covalent organic frameworks (COFs) have received extensive...
Photodynamic therapy (PDT) using two-photon near-infrared light excitation is a very effective way to avoid the use of shortwavelength ultraviolet or visible light which cannot efficiently penetrate into the biological tissues and is harmful to the healthy cells. Herein, a series of cyclometalated Ir(III) complexes with a structurally simple diimine ligand were designed and the synthetic route and preparation procedure were optimized, so that the complexes could be obtained in apparently higher yield, productivity, and efficiency in comparison to the traditional methods. Their ground state and excited singlet and triplet state properties were studied by spectroscopy and quantum chemistry theoretical calculations to investigate the effect of substituent groups on the photophysical properties of the complexes. The Ir(III) complexes, especially Ir1 and Ir3, showed very low dark toxicities and high phototoxicities under both one-photon and twophoton excitation, indicating their great potential as PDT agents. They were also found to be highly sensitive two-photon mitochondria dyes.
We take advantage of the folic acid conjugated iron-based metal–organic frameworks (Fe-MIL-101) without any surface modification to design a simple and sensitive colorimetric assay to detect cancer cells based on its intrinsic peroxidase-like activity over broad pH range.
Metals–organic
frameworks (MOFs) have been widely explored
in biomedicine, mostly in drug delivery, biosensing, and bioimaging
due to their large surface area, tunable porosity, readily chemical
functionalization, and good biocompatibility. However, the underlining
cellular mechanisms controlling the process for MOF cytotoxicity remains
almost completely unknown. Here, we demonstrate that pristine Cu-MOF
without any loaded drug selectively inhibited ovarian cancer mainly
through promoting tubulin polymerization and destroying the cell actin
cytoskeleton (F-actin) to trigger the mitotic catastrophe, accompanying
by conventional programmed cell death. To our knowledge, this is the
first report claiming that mitotic catastrophe may be an explaining
mechanism of MOF cytotoxicity. Cu-MOF with an intrinsic protease-like
activity also hydrolyzed cellular cytoskeleton proteins (F-actin).
The RNA sequencing data indicated the differential expressional mRNA
of cell proliferation and actin cytoskeleton (ACTA2, ACTN3, FSCN2,
and SCIN) and mitotic spindles (PLK1 and TPX2) related genes. We found
that Cu-MOF as a promising candidate in the disruption of cellular
cytoskeleton and the change of the gene expression could be actin
altering and antimitotic agents against cancer cells, allowing for
fundamental biological and biophysical studies of MOFs.
It was shown that some nanomaterials may have anticancer properties, but lack of selectivity is one of challenges, let alone selective suppression of cancer growth by regulating the cellular microenvironment. Herein, we demonstrated for the first time that carbon quantum dots/Cu2O composite (CQDs/Cu2O) selectively inhibited ovarian cancer SKOV3 cells by targeting cellular microenvironment, such as matrix metalloproteinases, angiogenic cytokines and cytoskeleton. The result was showed CQDs/Cu2O possessed anticancer properties against SKOV3 cells with IC50 = 0.85 μg mL−1, which was approximately threefold lower than other tested cancer cells and approximately 12-fold lower than normal cells. Compared with popular anticancer drugs, the IC50 of CQDs/Cu2O was approximately 114-fold and 75-fold lower than the IC50 of commercial artesunate (ART) and oxaliplatin (OXA). Furthermore, CQDs/Cu2O possessed the ability to decrease the expression of MMP-2/9 and induced alterations in the cytoskeleton of SKOV3 cells by disruption of F-actin. It also exhibited stronger antiangiogenic effects than commercial antiangiogenic inhibitor (SU5416) through down-regulating the expression of VEGFR2. In addition, CQDs/Cu2O has a vital function on transcriptional regulation of multiple genes in SKOV3 cells, where 495 genes were up-regulated and 756 genes were down-regulated. It is worth noting that CQDs/Cu2O also regulated angiogenesis-related genes in SKOV3 cells, such as Maspin and TSP1 gene, to suppress angiogenesis. Therefore, CQDs/Cu2O selectively mediated of ovarian cancer SKOV3 cells death mainly through decreasing the expression of MMP-2, MMP-9, F-actin, and VEGFR2, meanwhile CQDs/Cu2O caused apoptosis of SKOV3 via S phase cell cycle arrest. These findings reveal a new application for the use of CQDs/Cu2O composite as potential therapeutic interventions in ovarian cancer SKOV3 cells.
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