Rational design of metal-organic frameworks to deliver methotrexate for targeted rheumatoid arthritis therapy

Guo, Lin; Chen, Yang; Wang, Ting; Yuan, Yu; Yang, Yihua; Luo, Xin; Hu, Shuo; Ding, Jinsong; Zhou, Wenhu

doi:10.1016/j.jconrel.2020.10.069

Cited by 58 publications

(47 citation statements)

References 55 publications

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“…2 A), indicating a cell selective internalization of the nanoparticles. This can be attributable to the surface HA modification of the nanoparticles, which endows the specific recognition towards CD44 over-expressed M1 macrophages [ 36 ]. To validate this, we further pre-treated the M1 macrophages with free HA to compete CD44 binding, and in this case the fluorescence inside cells weakened obviously, demonstrating the crucial contribution of CD44-mediated intracellular delivery.…”

Section: Resultsmentioning

confidence: 99%

Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy

Sun

Yao

et al. 2022

J Nanobiotechnol

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Atherosclerosis (AS) is a leading cause of vascular diseases that severely threats the human health due to the lack of efficient therapeutic methods. During the development and progress of AS, macrophages play critical roles, which are polarized into pro-inflammatory M1 phenotype to excrete abundant cytokines and overproduce reactive oxygen species (ROS), and take up excess amount of lipid to form foam cells. In this work, we developed a MnO2-based nanomedicine to re-educate macrophages for targeting AS therapy. The MnO2 was one-pot synthesized under mild condition, showing intrinsic catalase-mimic activity for self-oxygenation by using endogenous H2O2 as substrate. Moreover, the mesoporous structure as well as the abundant metal coordination sites in MnO2 structure facilitated the loading of an anti-AS drug of curcumin (Cur), achieving extraordinarily high drug loading capacity of 54%. Cur displayed a broad spectrum of anti-oxidant and anti-inflammatory capabilities to repolarize M1 macrophages into M2 phenotype, and the catalytic MnO2 recovered the function of lipid efflux transporter to remove lipid from cells by suppressing HIF-1α. Collectively, the nanocarrier and the payload drug functioned as an all-active nanoplatform to synergistically alleviate the syndromes of AS. In ApoE−/− mice model, the nanosystem could significantly prolong the circulation half-life of Cur by sixfold, and enhance drug accumulation in atherosclerotic lesion by 3.5-fold after intravenous injection by virtue of surface hyaluronic acid (HA) modification. As a result, a robust anti-AS efficacy was achieved as evidenced by the decrease of atherosclerotic lesion, plaque area, lipid level. Graphical Abstract

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Section: Resultsmentioning

confidence: 99%

Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy

Sun

Yao

et al. 2022

J Nanobiotechnol

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“…1 A). MTX and MTX@ZIF-8 showed the same characteristic absorption peaks at 258 and 302 nm [ 48 ], indicating the successful loading of MTX into the ZIF-8 structure. Moreover, MTX@ZIF-8 showed a similar XRD pattern to ZIF-8, suggesting the negligible effect of MTX on the crystal structure of ZIF-8 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…MTX@ZIF-8, MV/MTX@ZIF-8, and FPD/MV/MTX@ZIF-8 were labeled with Rhm B and PKH67 according to the manufacturer’s protocol. Resting RAW264.7 cells or RAW264.7 cells stimulated for 24 h with LPS at a final concentration of 10 µg/mL were then incubated with the labeled formulations for 1 h at 37 °C [ 48 ]. After staining the cell nuclei with DAPI, endocytosis was observed by confocal laser scanning microscopy (Leica Microsystems, Wetzlar, Germany) [ 37 ].…”

Section: Methodsmentioning

confidence: 99%

Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy

et al. 2022

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Background Methotrexate (MTX) has been highlighted for Rheumatoid arthritis (RA) treatment, however, MTX does not accumulate well at inflamed sites, and long-term administration in high doses leads to severe side effects. In this study, a novel anti-RA nanoparticle complex was designed and constructed, which could improve the targeted accumulation in inflamed joints and reduce side effects. Results Here, we prepared a pH-sensitive biomimetic drug delivery system based on macrophage-derived microvesicle (MV)-coated zeolitic imidazolate framework-8 nanoparticles that encapsulated the drug methotrexate (hereafter MV/MTX@ZIF-8). The MV/MTX@ZIF-8 nanoparticles were further modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[folate (polyethylene glycol)-2000] (hereafter FPD/MV/MTX@ZIF-8) to exploit the high affinity of folate receptor β for folic acid on the surface of activated macrophages in RA. MTX@ZIF-8 nanoparticles showed high DLE (~ 70%) and EE (~ 82%). In vitro study showed that effective drug release in an acidic environment could be achieved. Further, we confirmed the activated macrophage could uptake much more FPD/MV/MTX@ZIF-8 than inactivated cells. In vivo biodistribution experiment displayed FPD/MV/MTX@ZIF-8 nanoparticles showed the longest circulation time and best joint targeting. Furthermore, pharmacodynamic experiments confirmed that FPD/MV/MTX@ZIF-8 showed sufficient therapeutic efficacy and safety to explore clinical applications. Conclusions This study provides a novel approach for the development of biocompatible drug-encapsulating nanomaterials based on MV-coated metal-organic frameworks for effective RA treatment. Graphical Abstract

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“… Sickness, numerous blood disorders, ulcers, mouth disorders and nausea. ( Valerio et al, 2021 , Guo et al, 2021 ) Myocrisin (GSTM), Auranofin Acts via inhibiting production of pro-inflammatory cytokines. Forms a complex with cysteine protease which prevents bone resorption and process of antigen presentation Mouth ulcers, blood disorder, kidney disorders, skin rashes, sore throat.…”

Section: Future Prospective: Therapeutic Approaches On Inhibiting the Action Of Cathepsinmentioning

confidence: 99%

Exploring the role of cathepsin in rheumatoid arthritis

Behl

Chadha

Sehgal

et al. 2022

Saudi Journal of Biological Sciences

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Rheumatoid arthritis (RA) is a chronic inflammatory disease which is marked by leukocytes infiltration inside synovial tissue, joints and also inside synovial fluid which causes progressive destruction of joint cartilage. There are numerous genetical and lifestyle factors, responsible for rheumatoid arthritis. One such factor can be cysteine cathepsins, which act as proteolytic enzymes. These proteolytic enzyme gets activated at acidic pH and are found in lysosomes and are also termed as cysteine proteases. These proteases belong to papain family and have their elucidated role in musculoskeletal disorders. Numerous cathepsins have their targeted role in rheumatoid arthritis. These proteases are secreted through various cell types which includes matrix metalloproteases and papain like cysteine proteases. These proteases can potentially lead to bone and cartilage destruction which causes an immune response in case of inflammatory arthritis.

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Rational design of metal-organic frameworks to deliver methotrexate for targeted rheumatoid arthritis therapy

Cited by 58 publications

References 55 publications

Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy

Self-oxygenation mesoporous MnO2 nanoparticles with ultra-high drug loading capacity for targeted arteriosclerosis therapy

Microvesicle-camouflaged biomimetic nanoparticles encapsulating a metal-organic framework for targeted rheumatoid arthritis therapy

Exploring the role of cathepsin in rheumatoid arthritis

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