Encapsulating doxorubicin in PEGylation metal-organic frameworks for combined radiation therapy in liver cancer treatment

2020 ◽  
Vol 10 (8) ◽  
pp. 1197-1203
Author(s):  
Dawei Liu ◽  
Bing Bai ◽  
Yanbin Sun ◽  
Youxin Guo
Keyword(s):  
Radiation Therapy ◽  
Drug Carrier ◽  
Drug Loading ◽  
Metal Organic Frameworks ◽  
Diagnosis And Treatment ◽  
X Rays ◽  
Chemotherapy Drugs ◽  
Metal Organic

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.

scholarly journals Kajian Metal–Organic Frameworks (MOFS) sebagai Material Baru Pengantar Obat

2018 ◽  
Vol 14 (1) ◽  
pp. 16
Author(s):  
Qonita Awliya Hanif ◽  
Reva Edra Nugraha ◽  
Witri Wahyu Lestari
Keyword(s):  
Electron Microscope ◽  
Drug Loading ◽  
Metal Organic Frameworks ◽  
X Ray Diffraction ◽  
Transmission Electron ◽  
Metal Organic ◽  
Post Synthesis ◽  
Grand Canonical

<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>

scholarly journals A Simple in vivo Assay Using Amphipods for the Evaluation of Potential Biocompatible Metal-Organic Frameworks

2021 ◽  
Vol 9 ◽  
Author(s):  
Ines Sifaoui ◽  
Idaira Pacheco-Fernández ◽  
José E. Piñero ◽  
Verónica Pino ◽  
Jacob Lorenzo-Morales
Keyword(s):  
Ex Vivo ◽  
Colorimetric Assay ◽  
Metal Organic Frameworks ◽  
Screening Method ◽  
Toxicity Tests ◽  
Toxicity Screening ◽  
Metal Organic ◽  
Potential Use

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.

131I-radioisotope modified in PEGylation metal organic frameworks for sensitization in refractory differentiated thyroid cancer treatment

2021 ◽  
pp. 088532822110298
Author(s):  
Shuai Jiang ◽  
Miao Yu ◽  
Haoyang Wang ◽  
Songqi Han ◽  
Mengfei Cheng ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Combined Therapy ◽  
Drug Loading ◽  
Metal Organic Frameworks ◽  
Local Therapy ◽  
Intratumoral Injection ◽  
Metal Organic ◽  
Local Tumour

Radiation therapy for cancer can lead to off-target toxicity and can be ineffective against refractory differentiated thyroid cancer. The nanoscale metal organic frameworks (NMOFs) have shown great potential in cancer diagnostic and treatment due to their advantages in the aspect of structural diversities, high intrinsic biodegradability and drug-loading capacities. Here, we provide that intratumoral injection, in mouse of refractory differentiated thyroid cancer. In this work, we used the therapeutic 131I radioisotope modified Zr-MOF (Zr-MOF@131I) with aim to enable long-term relief of tumour therapy, which has successfully eliminated tumour at ralatively low radioactivity doses. Polyethylene glycol (PEG) was coated into Zr-MOF and, as a result, circulation time was significantly improved by intratumoral injection. These findings therefore suggest that nanoparticles could be used in vivo combined therapy. On injection, while it is a highly effective drug for radioisotope, Zr-MOF with attenuation ability could apply for a radio-sensitizer to enhance inner radiotherapy (RT). The local therapy, which uses only biocompatible components, might enable new strategies for local tumour treatments. These could be further combined with systemic therapeutic responses for the inhibition of refractory differentiated thyroid cancer and the prevention of tumour recurrence in patients.

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

scholarly journals Chitosan overlaid Fe3O4/rGO nanocomposite for targeted drug delivery, imaging, and biomedical applications

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Viswanathan Karthika ◽  
Mohamad S. AlSalhi ◽  
Sandhanasamy Devanesan ◽  
Kasi Gopinath ◽  
Ayyakannu Arumugam ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Folic Acid ◽  
Targeted Drug Delivery ◽  
Drug Carrier ◽  
Drug Loading ◽  
Antioxidant Properties ◽  
Targeted Drug ◽  
Loading Amount

Abstract A hybrid and straightforward nanosystem that can be used simultaneously for cancer-targeted fluorescence imaging and targeted drug delivery in vitro was reported in this study. A chitosan (CS) polymer coated with reduced graphene oxide (rGO) and implanted with Fe3O4 nanoparticles was fabricated. The fundamental physicochemical properties were confirmed via FT-IR, XRD, FE-SEM, HR-TEM, XPS, and VSM analysis. The in vivo toxicity study in zebrafish showed that the nanocomposite was not toxic. The in vitro drug loading amount was 0.448 mg/mL−1 for doxorubicin, an anticancer therapeutic, in the rGO/Fe3O4/CS nanocomposite. Furthermore, the pH-regulated release was observed using folic acid. Cellular uptake and multimodal imaging revealed the benefit of the folic acid-conjugated nanocomposite as a drug carrier, which remarkably improves the doxorubicin accumulation inside the cancer cells over-express folate receptors. The rGO/Fe3O4/CS nanocomposite showed enhanced antibiofilm and antioxidant properties compared to other materials. This study's outcomes support the use of the nanocomposite in targeted chemotherapy and the potential applications in the polymer, cosmetic, biomedical, and food industries.

BODIPY-containing nanoscale metal–organic frameworks as contrast agents for computed tomography

2017 ◽  
Vol 5 (12) ◽  
pp. 2330-2336 ◽  
Author(s):  
Tao Zhang ◽  
Lei Wang ◽  
Chong Ma ◽  
Weiqi Wang ◽  
Jun Ding ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Contrast Agents ◽  
Metal Organic Frameworks ◽  
Ct Imaging ◽  
Imaging Agent ◽  
Metal Organic

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.

Methotrexate-loaded metal-organic frameworks on the basis of γ-cyclodextrin: Design, characterization, in vitro and in vivo investigation

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

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
Keyword(s):  
Small Molecule ◽  
Metal Organic Frameworks ◽  
Metal Organic

Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier

2018 ◽  
Vol 18 (2) ◽  
pp. 302-311
Author(s):  
Shulin Dai ◽  
Yucheng Feng ◽  
Shuyi Li ◽  
Yuxiao Chen ◽  
Meiqing Liu ◽  
...  
Keyword(s):  
Glutamic Acid ◽  
Drug Carrier ◽  
Drug Loading ◽  
Drug Carriers ◽  
Cancer Drug ◽  
Drug Release Profile ◽  
Sustained Drug Release ◽  
Anti Cancer ◽  
Physical Interactions

Background: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. </P><P> Aims/Methods: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. Result: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

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