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.

Folic acid decorated metal-organic frameworks loaded with doxorubicin for tumor-targeted chemotherapy of osteosarcoma

2020 ◽  
Vol 65 (2) ◽  
pp. 229-236
Author(s):  
Weifan Xu ◽  
Yi Lou ◽  
WangShenjie Chen ◽  
Yifan Kang
Keyword(s):  
Folic Acid ◽  
Folate Receptor ◽  
Xenograft Model ◽  
Drug Carriers ◽  
Synthesis Process ◽  
Scattering Method ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells ◽  
Metal Organic

AbstractEffective cancer therapy usually requires the assistance of well-designed drug carriers. In order to increase the drug accumulation to tumor tissue as well as to reduce the side effects of drug carriers, the hybrid drug delivery system (DDS) was developed by integrating folic acid (FA) and a metal-organic framework (MOF). The anticancer drug doxorubicin (DOX) was preloaded into the MOF nanoparticles during the synthesis process of the MOF nanoparticles. After surface modification with FA, the resulting FA/MOF/DOX nanoparticles were capable of serving as a biocompatible osteosarcoma targeting a DDS to enhance the chemotherapy of osteosarcoma. The dynamic light scattering method revealed that the obtained FA/MOF/DOX nanoparticles were particles with a size around 100 nm. Moreover, FA/MOF/DOX nanoparticles could enhance the delivery efficacy of DOX into MG63 (human osteosarcoma) cells as compared to FA free nanoparticles (MOF/DOX), in which a folate receptor (FR) might be involved. It was worth mentioning that in vitro [methylthio tetrazole (MTT) study in the MG63 cells] and in vivo (anticancer study in the MG63 xenograft model) assays both revealed that FA/MOF/DOX nanoparticles possessed stronger anticancer capability than free DOX or MOF/DOX nanoparticles.

scholarly journals Evaluating biological activity of folic acid-modified and 10-hydroxycamptothecin-loaded mesoporous silica nanoparticles

2021 ◽  
Author(s):  
Mei-Xia Zhao ◽  
Di-Feng Chen ◽  
Xue-Jie Zhao ◽  
Lin-Song Li ◽  
Yong-Fang Liu
Keyword(s):  
Folic Acid ◽  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Folate Receptor ◽  
Mesoporous Silica Nanoparticles ◽  
Drug Carriers ◽  
Transmission Electron ◽  
Before And After ◽  
Drug Efficiency

Targeted nanocarrier can selectively deliver anti-tumor drugs to cancer sites improving drug efficiency. Accordingly, a targeted nanocarrier (MSN-FA) was synthesized based on folic acid (FA) modified mesoporous silica nanoparticles (MSNs). These loaded with 10-hydroxycamptothecin (HCPT) to obtain the nano-drug MSN-FA@HCPT. These nanocarriers were characterized by transmission electron microscopy (TEM), zeta potential, ultraviolet-visible spectroscopy (UV-Vis), fourier transform infrared spectroscopy (FT-IR), and thermogravimetric analysis (TGA). Notably, the nanocarriers were nearly spherical before and after loading HCPT and exhibited good dispersibility. Also, folate receptor (FR) over-expressing HeLa cells and FR deficient HepG2 cells were used to evaluate in vitro cellular uptake and cytotoxicity of MSN-FA@HCPT and MSN@HCPT. Interestingly, FA-modified nanocarriers enhanced the cytotoxicity of HCPT by improving drug targeting to tumor cells. Also, apoptotic and mitochondrial membrane potential (MMP) reducing effects of MSN-FA@HCPT were more prominent than the MSNs without FA modification. MSN-FA@HCPT can be excellent drug carriers with profound biomedical applications.

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.

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 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.

scholarly journals Pharmacokinetic Properties of 68Ga-labelled Folic Acid Conjugates: Improvement Using HEHE Tag

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2712
Author(s):  
Anton Larenkov ◽  
Marat Rakhimov ◽  
Kristina Lunyova ◽  
Olga Klementyeva ◽  
Alesya Maruk ◽  
...  
Keyword(s):  
Folic Acid ◽  
Inflammatory Diseases ◽  
Folate Receptor ◽  
Renal Tissue ◽  
Laboratory Animals ◽  
Biodistribution Studies ◽  
Pharmacokinetic Properties ◽  
Normal Laboratory

The folate receptor (FR) is a promising cell membrane-associated target for molecular imaging and radionuclide therapy of cancer (FR-α) and potentially also inflammatory diseases (FR-β) through use of folic acid-based radioconjugate. FR is often overexpressed by cells of epithelial tumors, including tumors of ovary, cervix, endometrium, lungs, kidneys, etc. In healthy tissues, FR can be found in small numbers by the epithelial cells, mainly in the kidneys. Extremely high undesired accumulation of the folate radioconjugates in the renal tissue is a main drawback of FR-targeting concept. In the course of this work, we aimed to reduce the undesirable accumulation of folate radioconjugates in the kidneys by introducing a histidine/glutamic acid tag into their structure. Two folic acid based compounds were synthesized: NODAGA-1,4-butanediamine-folic acid (FA-I, as control) and NODAGA-[Lys-(HE)2]-folic acid (FA-II) which contains a (His-Glu)2 fragment. In vitro studies with FR (+) cells (KB and others) showed that both compounds have specificity for FR. Introduction of (HE)2-tag does not affect FR binding ability of the conjugates. In vivo biodistribution studies with normal laboratory animals, as well as with KB tumor bearing animals, were carried out. The results showed that introduction of the (HE)2 tag into the structure of folate radioconjugates can significantly reduce the accumulation of these compounds in non-target tissues and important organs (the accumulation in the kidneys is reduced 2–4 times), leaving the accumulation in tumor at least at the same level, and even increasing it.

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