scholarly journals Integrated cascade nanozyme catalyzes in vivo ROS scavenging for anti-inflammatory therapy

2020 ◽  
Vol 6 (29) ◽  
pp. eabb2695 ◽  
Author(s):  
Yufeng Liu ◽  
Yuan Cheng ◽  
He Zhang ◽  
Min Zhou ◽  
Yijun Yu ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Metal Organic Framework ◽  
Pt Nanoparticles ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Scavenging Capacity ◽  
Metal Organic ◽  
Inflammatory Bowel

Here, an integrated cascade nanozyme with a formulation of Pt@PCN222-Mn is developed to eliminate excessive reactive oxygen species (ROS). This nanozyme mimics superoxide dismutase by incorporation of a Mn–[5,10,15,20-tetrakis(4-carboxyphenyl)porphyrinato]–based metal-organic framework compound capable of transforming oxygen radicals to hydrogen peroxide. The second mimicked functionality is that of catalase by incorporation of Pt nanoparticles, which catalyze hydrogen peroxide disproportionation to water and oxygen. Both in vitro and in vivo experimental measurements reveal the synergistic ROS-scavenging capacity of such an integrated cascade nanozyme. Two forms of inflammatory bowel disease (IBD; i.e., ulcerative colitis and Crohn’s disease) can be effectively relieved by treatment with the cascade nanozyme. This study not only provides a new method for constructing enzyme-like cascade systems but also illustrates their efficient therapeutic promise in the treatment of in vivo IBDs.

scholarly journals Metal–Organic Framework-Based Chemo-Photothermal Combinational System for Precise, Rapid, and Efficient Antibacterial Therapeutics

Pharmaceutics ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 463 ◽  
Author(s):  
Wu ◽  
Fu ◽  
Zhou ◽  
Wang ◽  
Feng ◽  
...  
Keyword(s):  
Laser Irradiation ◽  
Photothermal Therapy ◽  
Metal Organic Framework ◽  
Global Public Health ◽  
Zeolitic Imidazolate Frameworks ◽  
Porous Carrier ◽  
Metal Organic ◽  
Organic Framework

Rapid increase of antimicrobial resistance has become an urgent threat to global public health. In this research, since photothermal therapy is a potential antibacterial strategy, which is less likely to cause resistance, a metal–organic framework-based chemo-photothermal combinational system was constructed. Zeolitic imidazolate frameworks-8 (ZIF-8), a porous carrier with unique features such as high loading and pH-sensitive degradation, was synthesized, and then encapsulated photothermal agent indocyanine green (ICG). First, ICG with improved stability in ZIF-8 (ZIF-8-ICG) can effectively produce heat in response to NIR laser irradiation for precise, rapid, and efficient photothermal bacterial ablation. Meanwhile, Zn2+ ions released from ZIF-8 can inhibit bacterial growth by increasing the permeability of bacterial cell membrane and further strengthen photothermal therapy efficacy by reducing the heat resistance of bacteria. Study showed that bacteria suffered from significant changes in morphology after treatment with ZIF-8-ICG under laser irradiation. The combinational chemo-hyperthermia therapy of ZIF-8-ICG could thoroughly ablate murine subcutaneous abscess induced by methicillin-resistant Staphylococcus aureus (MRSA), exhibiting a nearly 100% bactericidal ratio. Both in vitro and in vivo safety evaluation confirmed that ZIF-8-ICG was low toxic. Overall, our researches demonstrated that ZIF-8-ICG has great potential to be served as an alternative to antibiotics in combating multidrug-resistant bacterial pathogens.

Adriamycin Loaded and Folic Acid Coated Zn-MOF for Tumor-Targeted Chemotherapy of Cervical Cancer

2019 ◽  
Vol 9 (11) ◽  
pp. 1535-1541
Author(s):  
Jing Sun ◽  
Xiang-E Long ◽  
Rong Li ◽  
Chao-Feng Hu ◽  
Xiao-Hong Ge
Keyword(s):  
Folic Acid ◽  
Drug Targeting ◽  
Folate Receptor ◽  
Metal Organic Framework ◽  
Drug Carriers ◽  
Spherical Particles ◽  
Metal Organic ◽  
Cervical Tumors

The drug delivery systems (DDSs) introduced in recent years have been wide recognized to greatly evaluate the efficacy of drugs. With the aim to increase drug targeting to tumors as well as decrease the side effect of both drug and drug carriers, this study has developed a hybrid DDS by incorporation zinc based metal-organic framework (Zn-MOF) and folic acid (FA). Moreover, adriamycin (Adr) as a model anticancer drug was loaded into the FA/Zn-MOF nanoparticle. The as-prepared FA/ZnMOF/Adr was expected to serve as a tumor targeting DDS that capable of effectively delivering Adr to cervical tumors. Characterization revealed that FA/Zn-MOF/Adr was nanosized spherical particles with high stability and biocompatibility. Most importantly, the FA/Zn-MOF/Adr could realize positive targeting to FA overexpressed HeLa cells through folate receptor (FR). Therefore, FA/Zn-MOF/Adr resulted enhanced in vitro and in vivo anticancer benefits than than free Adr or FA unmodified Zn-MOF/Adr.

scholarly journals Folate Receptor-Targeting and Reactive Oxygen Species-Responsive Liposomal Formulation of Methotrexate for Treatment of Rheumatoid Arthritis

Pharmaceutics ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 582 ◽  
Author(s):  
Chen ◽  
Amerigos J.C. ◽  
Su ◽  
Guissi ◽  
Xiao ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Drug Release ◽  
Cellular Uptake ◽  
Folate Receptor ◽  
Oxygen Species ◽  
Activated Macrophages

Multifunctional nanomedicines with active targeting and stimuli-responsive drug release function utilizing pathophysiological features of the disease are regarded as an effective strategy for treatment of rheumatoid arthritis (RA). Under the inflammatory environment of RA, activated macrophages revealed increased expression of folate receptor and elevated intracellular reactive oxygen species (ROS) level. In this study, we successfully conjugated folate to polyethylene glycol 100 monostearate as film-forming material and further prepared methotrexate (MTX) and catalase (CAT) co-encapsulated liposomes, herein, shortened to FOL-MTX&CAT-L, that could actively target to activated macrophages. Thereafter, elevated intracellular hydrogen peroxide, the main source of ROS, diffused into liposomes and encapsulated CAT catalyzed the decomposition of hydrogen peroxide into oxygen and water. Continuous oxygen-generation inside liposomes would eventually disorganize its structure and release the encapsulated MTX. We characterized the in vitro drug release, cellular uptake and cytotoxicity studies as well as in vivo pharmacokinetics, biodistribution, therapeutic efficacy and safety studies of FOL-MTX&CAT-L. In vitro results revealed that FOL-MTX&CAT-L possessed sufficient ROS-sensitive drug release, displayed an improved cellular uptake through folate-mediated endocytosis and exhibited a higher cytotoxic effect on activated RAW264.7 cells. Moreover, in vivo results showed prolonged blood circulation time of PEGylated liposomes, enhanced accumulation of MTX in inflamed joints of collagen-induced arthritis (CIA) mice, reinforced therapeutic efficacy and minimal toxicity toward major organs. These results imply that FOL-MTX&CAT-L may be used as an effective nanomedicine system for RA treatment.

scholarly journals γ-Cyclodextrin Metal-Organic Framework as a Carrier to Deliver Triptolide for the Treatment of Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhe Li ◽  
Gang Yang ◽  
Rong Wang ◽  
Yuanyuan Wang ◽  
Jing Wang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Water Solubility ◽  
Metal Organic Framework ◽  
Cell Internalization ◽  
The Poor ◽  
Metal Organic ◽  
Tumor Drugs ◽  
Organic Framework

Abstract Triptolide (TPL) has been employed to treat hepatocellular carcinoma (HCC). However, the poor water-solubility of TPL restrict its applications. Therefore, we prepared TPL loaded cyclodextrin-based metal-organic framework (TPL@CD-MOF) to improve the solubility and bioavailability of TPL, thus enhancing the anti-tumor effect on HCC. The BET surface and the pore size of TPL@CD-MOF were 1134.5 m2·g−1 and 1.6 nm, respectively. The results of XRD indicated that TPL in TPL@CD-MOF was encapsuled. TPL@CD-MOF showed a slower release than free TPL in vitro. Moreover, the CD-MOF improved the cell internalization and bioavailability of TPL. TPL@CD-MOF also showed higher anti-tumor efficacy in vitro and in vivo compared to free TPL. As a carrier, CD-MOF improved the solubility and bioavailability of TPL. In addition, TPL@CD-MOF exhibited improved anti-tumor effects in vitro and in vivo, indicating great potential as a carrier for insoluble anti-tumor drugs.

scholarly journals Biomimetic Metal-organic Framework Nanoparticles for Synergistic Combining of SDT-chemotherapy Induce Pyroptosis in Gastric Cancer

2021 ◽  
Author(s):  
zhu yu ◽  
Wenlong Cao ◽  
Chuangye Han ◽  
Zhen Wang ◽  
Yue Qiu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Targeted Delivery ◽  
Metal Organic Framework ◽  
Ultrasound Irradiation ◽  
Non Invasive ◽  
In Vivo Experiments ◽  
Metal Organic ◽  
Zeolitic Imidazole Frameworks

Abstract In recent years, sonodynamic therapy (SDT) has been widely developed for cancer research as a promising non-invasive therapeutic strategy. Here, we synthesized Zeolitic imidazole frameworks-8 (ZIF-8) and utilized its properties to encapsulate hydrophobic Chlorin e6 (Ce6) and hydrophilic tirapazamine (TPZ) for a synergistic sonodynamic-chemotherapy, which was also accompanied by the modification of cytomembrane of gastric cancer (GC) cells. Thus, we enabled the biomimetic property to achieve targeted delivery. Ce6-mediated SDT, in combination with ultrasound irradiation, could target the release of reactive oxygen species (ROS) to aggravate further hypoxia, which activated TPZ. Combining these effects could induce the pyroptosis of GC cells. Both in vitro and in vivo experiments showed that the nanoparticle had good biocompatibility and anti-cancer function, which could provide a potential therapeutic method for cancer therapy.

Metal-organic framework-encapsulated nanoparticles for synergetic chemo/chemo-dynamic therapy with targeted H2O2 self-supplying

2021 ◽  
Author(s):  
Ruixue Cui ◽  
Jing Shi ◽  
Zhiliang Liu
Keyword(s):  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Cancer Therapy ◽  
Therapeutic Strategy ◽  
Metal Organic Framework ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Dynamic Therapy ◽  
Metal Organic ◽  
Encapsulated Nanoparticles

Nanocatalytic cancer therapy based on chemo-dynamic therapy, which converts hydrogen peroxide (H2O2) into toxic reactive oxygen species via Fenton-like reaction, is regarded as a promising therapeutic strategy due to its...

scholarly journals Polydopamine-coated UiO-66 nanoparticles loaded with perfluorotributylamine/tirapazamine for hypoxia-activated osteosarcoma therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Hongfang Chen ◽  
You Fu ◽  
Kai Feng ◽  
Yifan Zhou ◽  
Xin Wang ◽  
...  
Keyword(s):  
Metal Organic Framework ◽  
Drug Carrier ◽  
Intratumoral Injection ◽  
Enhanced Permeability And Retention ◽  
Tail Vein Injection ◽  
Tumor Tissues ◽  
Metal Organic ◽  
Tumor Region

Abstract Background Hypoxia is a characteristic of solid tumors that can lead to tumor angiogenesis and early metastasis, and addressing hypoxia presents tremendous challenges. In this work, a nanomedicine based on oxygen-absorbing perfluorotributylamine (PFA) and the bioreductive prodrug tirapazamine (TPZ) was prepared by using a polydopamine (PDA)-coated UiO-66 metal organic framework (MOF) as the drug carrier. Results The results showed that TPZ/PFA@UiO-66@PDA nanoparticles significantly enhanced hypoxia, induced cell apoptosis in vitro through the oxygen-dependent HIF-1α pathway and decreased oxygen levels in vivo after intratumoral injection. In addition, our study demonstrated that TPZ/PFA@UiO-66@PDA nanoparticles can accumulate in the tumor region after tail vein injection and effectively inhibit tumor growth when combined with photothermal therapy (PTT). TPZ/PFA@UiO-66@PDA nanoparticles increased HIF-1α expression while did not promote the expression of CD31 in vivo during the experiment. Conclusions By using TPZ and PFA and the enhanced permeability and retention effect of nanoparticles, TPZ/PFA@UiO-66@PDA can target tumor tissues, enhance hypoxia in the tumor microenvironment, and activate TPZ. Combined with PTT, the growth of osteosarcoma xenografts can be effectively inhibited. Graphic abstract

3D printing of metal–organic framework incorporated porous scaffolds to promote osteogenic differentiation and bone regeneration

Nanoscale ◽  
2020 ◽  
Vol 12 (48) ◽  
pp. 24437-24449
Author(s):  
Linna Zhong ◽  
Junyu Chen ◽  
Zhiyong Ma ◽  
Hao Feng ◽  
Song Chen ◽  
...  
Keyword(s):  
3D Printing ◽  
Bone Regeneration ◽  
Osteogenic Differentiation ◽  
Composite Scaffold ◽  
Metal Organic Framework ◽  
Porous Scaffolds ◽  
Porous Composite ◽  
Metal Organic

A nanoZIF-8 modified porous composite scaffold was fabricated via extrusion-based 3D printing technology, which could promote osteogenesis in vitro and accelerate bone regeneration in vivo.

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