Tuning the Endocytosis Mechanism of Zr-Based Metal–Organic Frameworks through Linker Functionalization

Orellana-Tavra, Claudia; Haddad, Salame; Marshall, Ross J.; Lázaro, Isabel Abánades; Boix, Gerard; Imaz, Inhar; Maspoch, Daniel; Forgan, Ross S.; Fairen‐Jimenez, David

doi:10.1021/acsami.7b07342

Cited by 51 publications

(63 citation statements)

References 62 publications

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“…As all the cal@NMOF samples were prepared from the same base batch, we assume that variations are caused by changes in external surface chemistry, not particle size, in concert with our previous work which shows particle size has only minor effect until sizes >500 nm are reached. 34 Uptake efficiency was analysed after incubating cells with a fixed NMOF concentration (0.5 mgmL -1 ), normalising the data to UiO-66-L1 cell internalisation, taking into account differing calcein loading values ( Figure 5a). In general, cal@UiO-66 uptake is highly efficient compared to free calcein (6-10 fold increase), proving the validity of NMOFs as carriers to internalise cargo not able to efficiently cross the cell membrane by themselves.…”

Section: Endocytosis Efficiencies and Routes Of Surface-modified Uio-66mentioning

confidence: 99%

Mechanistic Investigation into the Selective Anticancer Cytotoxicity and Immune System Response of Surface-Functionalized, Dichloroacetate-Loaded, UiO-66 Nanoparticles

Lázaro

Haddad

Rodrigo‐Muñoz

et al. 2018

ACS Appl. Mater. Interfaces

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The high drug-loading and excellent biocompatibilities of metal-organic frameworks (MOFs) have led to their application as drug-delivery systems (DDSs). Nanoparticle surface chemistry dominates both biostability and dispersion of DDSs while governing their interactions with biological systems, cellular and/or tissue targeting, and cellular internalization, leading to a requirement for versatile and reproducible surface functionalization protocols. Herein, we explore not only the effect of introducing different surface functionalities to the biocompatible Zr-MOF UiO-66 but also the efficacy of three surface modification protocols: (i) direct attachment of biomolecules [folic acid (FA) and biotin (Biot)] introduced as modulators for UiO-66 synthesis, (ii) our previously reported "click-modulation" approach to covalently attach polymers [poly(ethylene glycol) (PEG), poly-l-lactide, and poly-N-isopropylacrylamide] to the surface of UiO-66 through click chemistry, and (iii) surface ligand exchange to postsynthetically coordinate FA, Biot, and heparin to UiO-66. The innovative use of a small molecule with metabolic anticancer activity, dichloroacetate (DCA), as a modulator during synthesis is described, and it is found to be compatible with all three protocols, yielding surface-coated, DCA-loaded (10-20 w/w %) nano-MOFs (70-170 nm). External surface modification generally enhances the stability and colloidal dispersion of UiO-66. Cellular internalization routes and efficiencies of UiO-66 by HeLa cervical cancer cells can be tuned by surface chemistry, and anticancer cytotoxicity of DCA-loaded MOFs correlates with the endocytosis efficiency and mechanisms. The MOFs with the most promising coatings (FA, PEG, poly-l-lactide, and poly-N-isopropylacrylamide) were extensively tested for selectivity of anticancer cytotoxicity against MCF-7 breast cancer cells and HEK293 healthy kidney cells as well as for cell proliferation and reactive oxygen species production against J774 macrophages and peripheral blood lymphocytes isolated from the blood of human donors. DCA-loaded, FA-modified UiO-66 selectively kills cancer cells without harming healthy ones or provoking immune system response in vitro, suggesting a significant targeting effect and great potential in anticancer drug delivery. The results provide mechanistic insight into the design and functionalization of MOFs for drug delivery and underline the availability of various in vitro techniques to potentially minimize early-stage in vivo animal studies following the three Rs: reduction, refinement, and replacement.

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Section: Endocytosis Efficiencies and Routes Of Surface-modified Uio-66mentioning

confidence: 99%

Mechanistic Investigation into the Selective Anticancer Cytotoxicity and Immune System Response of Surface-Functionalized, Dichloroacetate-Loaded, UiO-66 Nanoparticles

Lázaro

Haddad

Rodrigo‐Muñoz

et al. 2018

ACS Appl. Mater. Interfaces

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“…The favorable mesopore structure could provide the efficient transport pathways for the ILs and confine ILs in nanospace, both of which are beneficial for the interaction between ILs and additive. [ 45 ] The molecule structure were optimized at the B3LYP/6‐31G* level of theory by QM calculation and the geometry size of the cation and anion is 5.969 × 3.944 × 3.612 Å and 5.088 × 3.575 × 3.465 Å, respectively. [ 46 ] The more mesopores could make the ILs enter ZIF‐67/GO more easily, [ 47 ] which could contribute to quickly and efficiently adsorb ILs on ZIF‐67/GO through H‐bonding between ILs and ZIF‐67/GO and electrostatic interaction between IL's anion and Co 2+ in ZIF‐67.…”

Section: Resultsmentioning

confidence: 99%

Stable Dispersed Zeolitic Imidazolate Framework/Graphene Oxide Nanocomposites in Ionic Liquids Resulting in High Lubricating Performance

Cao

Zhuang

et al. 2020

Adv Materials Inter

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The “block‐on‐plate” nanocomposite structure material is realized with the zeolitic imidazolate framework (ZIF‐67) on graphene oxide (GO) with surface oxygen‐rich functional groups. Scanning electron microscopy, X‐ray photoelectron spectroscopy, X‐ray diffractograms, fourier transform infrared spectroscopy, and ZIF‐67/GO demonstrate a high capability of promoting the lubricating performance of [Choline][Proline] ([CH][P]) bio‐ionic liquid. Specifically, the wear volume of the disc by [CH][P]‐0.1 ZIF‐67/GO is only 52% of the one lubricated by pure [CH][P]. Moreover, ZIF‐67/GO shows a long time, high dispersion stability in [CH][P]. In addition, the combination of GO nanosheets and ZIF‐67 can make ZIF‐67/GO have better polishing effect between the steels during the friction process, which can effectively form a robust lubrication layer and improves overall lubricating properties. As a result, the interfacial lubrication can be significantly improved by these newly developed [CH][P]‐ZIF‐67/GO lubricants. This work offers a new promising application for ZIF‐67 nanocomposites with GO in advanced lubrication systems. This work also provides a new strategy of producing lubricants containing nanoparticles with high dispersion stability, which may solve the biggest challenge in this field.

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“…of NMOFs . Despite various degrees of improvement in NMOFs properties, it still remains a major challenge to obtain the stable and long‐circulating NMOFs for their in vivo administration …”

Section: Introductionmentioning

confidence: 99%

Highly Stable and Long‐Circulating Metal‐Organic Frameworks Nanoprobes for Sensitive Tumor Detection In Vivo

Zhang

Qiao

Jia

et al. 2019

Adv Healthcare Materials

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High stability and extended circulation time in vivo are quite favorable for practical biomedical applications of nanomaterials, because they greatly facilitate the preferential tumor accumulation of nanomaterials, resulting in enhanced signal fidelity for imaging and improved therapeutic effect for treatment. Although many surface modification approaches have been employed to improve the stability and circulating behavior of nanomaterials, it still remains challenging in acquiring stable and long‐lasting nanomaterials for in vivo bioimaging and therapy, especially for nanoscale metal‐organic frameworks (NMOFs) due to their intrinsic instability in physiological conditions. Herein, a facile, one‐step strategy is reported to encapsulate the zirconium (Zr)‐based NMOF UiO‐66 within 1,2‐dioleoyl‐sn‐glycero‐3‐phosphate (DOPA) lipid bilayer (DOPA‐LB). Contrary to UiO‐66 NMOFs functionalized with polyethylene glycol, the obtained UiO‐66@DOPA‐LB presents significantly enhanced stability and impressive blood circulation time, allowing a higher accumulation of UiO‐66@DOPA‐LB in the tumor tissue. Benefited from these meritorious features, UiO‐66@DOPA‐LB labeled with near‐infrared dye, IRDye 800CW, can not only achieve highly sensitive imaging of breast cancer tumor (5 mm), but also exhibits superior capability for early tumor (1–2 mm) detection. This study enriches the surface modification approach of NMOFs, and is of great importance for practical application of NMOFs in biomedical areas.

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Tuning the Endocytosis Mechanism of Zr-Based Metal–Organic Frameworks through Linker Functionalization

Cited by 51 publications

References 62 publications

Mechanistic Investigation into the Selective Anticancer Cytotoxicity and Immune System Response of Surface-Functionalized, Dichloroacetate-Loaded, UiO-66 Nanoparticles

Mechanistic Investigation into the Selective Anticancer Cytotoxicity and Immune System Response of Surface-Functionalized, Dichloroacetate-Loaded, UiO-66 Nanoparticles

Stable Dispersed Zeolitic Imidazolate Framework/Graphene Oxide Nanocomposites in Ionic Liquids Resulting in High Lubricating Performance

Highly Stable and Long‐Circulating Metal‐Organic Frameworks Nanoprobes for Sensitive Tumor Detection In Vivo

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