Metal-organic frameworks for simultaneous gene and small molecule delivery in vitro and in vivo

2021 ◽  
pp. 129386
Author(s):  
A. Ringaci ◽  
A.V. Yaremenko ◽  
K.G. Shevchenko ◽  
S.D. Zvereva ◽  
M.P. Nikitin
Author(s):  
Ines Sifaoui ◽  
Idaira Pacheco-Fernández ◽  
José E. Piñero ◽  
Verónica Pino ◽  
Jacob Lorenzo-Morales

In this study, the application of amphipods in vivo assays was evaluated. The main aim of this work was to check the potential use of this model in biocompatibility assessments of metal-organic frameworks (MOFs). Hence, six different MOFs were synthesized and the in vitro and ex vivo cytotoxicity was first assessed using a colorimetric assay and a macrophage cell line. Obtained results were compared to validate the in vivo toxicity tests carried out using amphipods and increasing concentrations of the different MOFs. Amphipods do not require the need of ethics approval and also are less expensive to keep than conventional in vivo models, showing its potential as a fast and reliable platform in toxicity studies. The obtained results showed that the amphipods based-assay was simple, easy to replicate and yielded toxicity data corresponding to the type of MOFs tested. In addition, it was observed that only CIM-80(Al) and CIM-84(Zr) did not show any toxicity to the animals at the different tested concentrations. Therefore, the developed in vivo model could be applied as a high-throughput toxicity screening method to evaluate the toxicity of numerous materials, chemicals and therapeutic agents among others.


2020 ◽  
Vol 10 (8) ◽  
pp. 1197-1203
Author(s):  
Dawei Liu ◽  
Bing Bai ◽  
Yanbin Sun ◽  
Youxin Guo

It is well known that nanoscale metal-organic frameworks (NMOFs) have exhibited brilliant advantages in cancer diagnosis and treatment due to their structural diversity, high intrinsic biodegradability, and drug-loading capacities. Herein, based on our previous results, hypoxia was suppressed by inhibiting the expression of the CA IX protein, produced from Zr-MOF nanoparticles, and enhancing radiation therapy (RT) effectiveness. We designed a nanocomposite by encapsulating doxorubicin into Zr-MOF nanoparticles. It is a highly effective drug for chemotherapy and MOF that can absorb X-rays well, applied to enhance RT as the radiosensitizer. PEG is used for surface modification in the nanoparticles and to improve circulation time by intravenous administration. These nanoparticles could be applied for RT combing with chemotherapy in vitro and vivo, obtaining excellent anticancer efficacy. Most importantly, Zr-MOF@Dox demonstrates high clearance from HepG2 tumor cells, reducing the circulation of toxicity in vivo. Our research exhibits a new approach to establishing Zr-MOF@Dox as a biodegradable drug-carrier system, containing chemotherapy drugs and functional elements that totally perform the diagnosis and treatment roles of RT.


2017 ◽  
Vol 5 (12) ◽  
pp. 2330-2336 ◽  
Author(s):  
Tao Zhang ◽  
Lei Wang ◽  
Chong Ma ◽  
Weiqi Wang ◽  
Jun Ding ◽  
...  

A new computed tomography (CT) imaging agent is developed based on the BODIPY-containing nanoscale metal–organic frameworks (NMOFs). The bio-safety and CT imaging of such NMOFs have been well investigated both in vitro and in vivo.


2020 ◽  
Vol 111 ◽  
pp. 110774 ◽  
Author(s):  
Iliya Kritskiy ◽  
Tatyana Volkova ◽  
Tatyana Sapozhnikova ◽  
Anton Mazur ◽  
Peter Tolstoy ◽  
...  

2018 ◽  
Vol 14 (1) ◽  
pp. 16
Author(s):  
Qonita Awliya Hanif ◽  
Reva Edra Nugraha ◽  
Witri Wahyu Lestari

<p><em>Metal–Organic Frameworks</em> (MOFs) merupakan material berpori baru yang berpotensi sebagai pengantar dan pelepas lambat obat. Strukturnya yang fleksibel, ukuran pori kristalin yang teratur, dan sisi koordinasi yang beragam merupakan beberapa kelebihan dari MOFs yang mendukung dalam enkapsulasi berbagai obat. Metode yang dapat digunakan untuk sintesis MOFs diantaranya nanopresipitasi, <em>solvothermal</em>, <em>reverse microemulsion</em>, dan reaksi <em>solvothermal</em> dengan template surfaktan. Karakterisasi material hasil sintesis maupun profil setelah enkapsulasi (<em>loading</em>) dapat dilakukan menggunakan <em>Scanning Electron Micrscope</em> (SEM), <em>Transmission Electron Microscope</em> (TEM), <em>Differential Scanning Calorymetry</em> (DSC), <em>Fourier Transform Infra Red Spectroscopy</em> (FTIR), dan <em>Powder X-Ray Diffraction </em>(PXRD). Metode <em>loading</em> obat terdiri dari dua kategori, yakni penggabungan agen biomedis secara langsung dan <em>loading</em> secara <em>post synthesis</em>. Sebelum MOFs diaplikasikan, perlu dilakukan aktivasi dan penempelan material obat. Pengujian lepas lambat dapat dijalankan pada beberapa kondisi seperti dalam <em>Simulated Body Fluid</em> (SBF), <em>Phosphate Buffer Saline</em> (PBS), <em>Bovine Serum Albumin</em> (BSA) maupun simulasi menggunakan <em>Grand Canonical Monte Carlo</em> (GCMC). Pengujian secara <em>in vivo</em> dan <em>in vitro</em> juga dapat dilakukan untuk mengetahui dampaknya pada tubuh makhluk hidup dan aktivitasnya terhadap sel patogen. Kombinasi organik <em>linker</em> dan ion logam pusat yang berbeda akan menghasilkan ukuran pori, fleksibilitas, kapasitas <em>loading</em>, profil pelepasan obat, toksisitas, dan kemampuan menginhibisi yang berbeda pula. Pada review kali ini akan dibahas tentang kajian singkat terkait struktur dan desain MOFs, bio-MOFs, nano bio MOFs, strategi sintesis, dan strategi <em>loading</em> dan pelepasan obat untuk aplikasi dalam biomedis. Selanjutnya akan diberikan beberapa contoh aplikasi yang sudah dilakukan sejauh ini misalnya beberapa jenis MOFs yang sudah dienkapsulasi dengan beberapa material obat, seperti 5-fluoracil, ibuprofen, doxorubicin, dan dikaji waktu pelepasannya dan interaksinya dengan permodelan komputasi.</p><p><strong>Study of Metal–Organic Frameworks (M</strong><strong>OF</strong><strong>s) as </strong><strong>a</strong><strong> Novel Material for Drug Delivery</strong>. Metal–Organic Frameworks (MOFs) are a novel class of porous material that has wide potential applications including in drug delivery and slow release. Its flexible structure, regular crystalline pore size, and various coordination sites are some of the advantages of supporting MOFs properties in the encapsulation of various drugs. Various methods can be used for the MOFs synthesis include nanoprecipitation, solvothermal, reverse micro emulsion, and surfactant-templated solvothermal. Both characterization for synthesized materials and profile after encapsulation can be done using Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM), Differential Scanning Calorimetry (DSC), Fourier Transform Infra-Red Spectroscopy (FTIR), and Powder X-Ray Diffraction (PXRD). The drug loading method consists of two categories, namely the direct incorporation of biomedical agents and post-synthesis method. Before MOFs are applied in biomedical application, activation and attachment of medicinal materials should be performed. Meanwhile, for slow release testing can be run on several conditions such as in Simulated Body Fluid (SBF), Phosphate Buffer Saline (PBS), Bovine Serum Albumin (BSA) and simulation using Grand Canonical Monte Carlo (GCMC). In vivo and in vitro testing can also be done to determine the impact on the body of living creatures and their activity on pathogen cells. Different organic linker and metal center combinations will result in pore size, flexibility, loading capacity, drug release profiles, toxicity, and different inhibiting ability. Herein, we will discuss a brief review of the structure and design of MOFs, bio-MOFs, nano-bio MOFs, synthesis, drug loading and release strategies for applications in biomedicine. Furthermore, there will be some examples of applications that have been done so far, e.g. some types of MOFs that have been encapsulated with some medicinal materials, such as 5-fluorouracil, ibuprofen, doxorubicin, and reviewed its release time and interaction with computational modeling.</p>


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Guodong Li ◽  
Chung-Nga Ko ◽  
Dan Li ◽  
Chao Yang ◽  
Wanhe Wang ◽  
...  

AbstractImpaired wound healing and ulcer complications are a leading cause of death in diabetic patients. In this study, we report the design and synthesis of a cyclometalated iridium(III) metal complex 1a as a stabilizer of hypoxia-inducible factor-1α (HIF-1α). In vitro biophysical and cellular analyses demonstrate that this compound binds to Von Hippel-Lindau (VHL) and inhibits the VHL–HIF-1α interaction. Furthermore, the compound accumulates HIF-1α levels in cellulo and activates HIF-1α mediated gene expression, including VEGF, GLUT1, and EPO. In in vivo mouse models, the compound significantly accelerates wound closure in both normal and diabetic mice, with a greater effect being observed in the diabetic group. We also demonstrate that HIF-1α driven genes related to wound healing (i.e. HSP-90, VEGFR-1, SDF-1, SCF, and Tie-2) are increased in the wound tissue of 1a-treated diabetic mice (including, db/db, HFD/STZ and STZ models). Our study demonstrates a small molecule stabilizer of HIF-1α as a promising therapeutic agent for wound healing, and, more importantly, validates the feasibility of treating diabetic wounds by blocking the VHL and HIF-1α interaction.


Author(s):  
Ayushi Singh ◽  
Ashish Kumar Singh ◽  
Jian-Qiang Liu ◽  
Abhinav Kumar

Metal-organic frameworks (MOFs) or coordination polymers (CPs) are regarded as new variety of materials that find potential applications in plethora of areas such as gas/small molecule absorption/separation, gas storage, membranes...


Sign in / Sign up

Export Citation Format

Share Document