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1.
Chem Sci ; 13(4): 934-944, 2022 Jan 26.
Article in English | MEDLINE | ID: mdl-35211258

ABSTRACT

The human body is in a never-ending chess game against pathogens. When the immune system, our natural defence tool, is weakened, these organisms are able to escape, overcoming the body's contingency plan, which results in the body going into a pathological state. To overcome this checkmate status, emerging nanomedicines have been successfully employed as one of the best tactics for boosting the immune response, manipulating the body's defence tools for the specific recognition/elimination of pathological cells via the active ingredient delivery. However, the vast majority of these drug-delivery systems (DDS) are considered to be exclusively passive vehicles, with nanoscale metal-organic frameworks (nanoMOFs) attracting a great deal of attention due to their versatility and ability to carry and deliver exceptional drug payloads and to modulate their biological bypass. Nonetheless, their intrinsic immunogenicity character has been never addressed. Considering the immense possibilities that nanoMOFs offer as a treatment platform, the present study aimed to unveil the immunological fingerprint of MOFs, including an in-deep evaluation of the cellular oxidation balance, the inflammation and recruitment of immune cells and the precise Th1/Th2 cytokine profile that is triggered. This study aims to gain insights that will make more feasible the design of customized immune-active MOF nanoplatforms according to targeted diseases, as the next ace up immune system sleeve.

2.
Nanoscale ; 12(8): 4839-4845, 2020 Feb 27.
Article in English | MEDLINE | ID: mdl-32065596

ABSTRACT

Despite the great interest in RNA therapeutics, the development of a successful gene delivery process is still a major challenge. We propose an efficient nucleic acid entrapment into the mesopores of biocompatible nanoscaled metal-organic frameworks. Their rapid cellular uptake together with RNA protection and release led to a relevant in vitro gene activity.


Subject(s)
Drug Carriers , Gene Transfer Techniques , Iron , Metal-Organic Frameworks , RNA , Cell Line, Tumor , Drug Carriers/chemistry , Drug Carriers/pharmacokinetics , Drug Carriers/pharmacology , Humans , Iron/chemistry , Iron/pharmacokinetics , Iron/pharmacology , Metal-Organic Frameworks/chemistry , Metal-Organic Frameworks/pharmacokinetics , Metal-Organic Frameworks/pharmacology , RNA/chemistry , RNA/pharmacokinetics , RNA/pharmacology
3.
Eur J Pharm Biopharm ; 132: 11-18, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30179739

ABSTRACT

Due to their high porosity and versatile composition and structure, nanoscaled Metal-Organic Frameworks (nanoMOFs) have been recently proposed as novel drug delivery systems, and have been demonstrated to have important capacities and potential for controlled release of different active ingredients. Gentamicin (GM; a broad spectrum aminoglycoside antibiotic indicated in bacterial septicemia therapy) has great therapeutic interest, but the associated bioavailability and toxicity drawbacks accompanying high doses and repeated administration of this free drug make its encapsulation inside new nanocarriers necessary. GM encapsulation within two different porous biofriendly Fe and Zr-carboxylates nanoMOFs was performed by a simple impregnation method, with full characterization of the resulting GM-containing solid using a large panel of techniques (X ray powder diffraction-XRPD, Fourier transform infrared spectroscopy-FTIR, thermogravimetric analysis-TGA, N2 sorption, scanning electron microscopy-SEM, dynamic light scattering-DLS, ζ-potential, fluorescence spectroscopy and molecular simulations). High reproducible encapsulation rates, reaching 600 µg of GM per·mg of formulation, were obtained using the biocompatible mesoporous iron(III) trimesate nanoparticles (NPs) MIL-100(Fe) (MIL: Materials from Institut Lavoisier). In vitro GM delivery studies were also carried out using different oral and intravenous simulated physiological conditions, with complete antibiotic release within 8 h when using protein free media, but lower release rates in the presence of proteins. Furthermore, in vitro toxicity of GM-containing MIL-100(Fe) NPs was investigated on two different cell lines: a monocyte from leukemia (THP-1) and adherent fibroblastoid cells (NIH/3T3). These nanoMOFs had a low cytotoxic profile with IC50 values up to 1 mg·mL-1, ensuring adequate cell proliferation after 24 h. Finally, antibacterial activity studies were carried out on two Gram-positive bacteria and one Gram-negative bacterium: S. aureus, S. epidermidis and P. aeruginosa, respectively. GM-loaded MIL-100(Fe) NPs exhibited the same activity as free GM, confirming that the antibiotic activity of the released GM was conserved.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Drug Delivery Systems , Gentamicins/administration & dosage , Metal Nanoparticles , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Delayed-Action Preparations , Gentamicins/pharmacology , Gentamicins/toxicity , Humans , Inhibitory Concentration 50 , Iron/chemistry , Metal-Organic Frameworks/chemistry , Mice , Microbial Sensitivity Tests , NIH 3T3 Cells , Porosity , Pseudomonas aeruginosa/drug effects , Staphylococcus aureus/drug effects , Staphylococcus epidermidis/drug effects , THP-1 Cells , Toxicity Tests/methods , Zirconium/chemistry
4.
Sci Rep ; 7: 43099, 2017 03 03.
Article in English | MEDLINE | ID: mdl-28256600

ABSTRACT

Nanometric biocompatible Metal-Organic Frameworks (nanoMOFs) are promising candidates for drug delivery. Up to now, most studies have targeted the intravenous route, related to pain and severe complications; whereas nanoMOFs for oral administration, a commonly used non-invasive and simpler route, remains however unexplored. We propose here the biofriendly preparation of a suitable oral nanocarrier based on the benchmarked biocompatible mesoporous iron(III) trimesate nanoparticles coated with the bioadhesive polysaccharide chitosan (CS). This method does not hamper the textural/structural properties and the sorption/release abilities of the nanoMOFs upon surface engineering. The interaction between the CS and the nanoparticles has been characterized through a combination of high resolution soft X-ray absorption and computing simulation, while the positive impact of the coating on the colloidal and chemical stability under oral simulated conditions is here demonstrated. Finally, the intestinal barrier bypass capability and biocompatibility of CS-coated nanoMOF have been assessed in vitro, leading to an increased intestinal permeability with respect to the non-coated material, maintaining an optimal biocompatibility. In conclusion, the preservation of the interesting physicochemical features of the CS-coated nanoMOF and their adapted colloidal stability and progressive biodegradation, together with their improved intestinal barrier bypass, make these nanoparticles a promising oral nanocarrier.


Subject(s)
Chitosan/metabolism , Enterocytes/metabolism , Nanoparticles/chemistry , Administration, Oral , Caco-2 Cells , Chitosan/administration & dosage , Chitosan/chemistry , Drug Liberation , Ferric Compounds/chemistry , Humans , Kinetics , Lysergic Acid Diethylamide/analogs & derivatives , Lysergic Acid Diethylamide/chemistry
5.
J Mater Chem B ; 5(14): 2560-2573, 2017 Apr 14.
Article in English | MEDLINE | ID: mdl-32264034

ABSTRACT

One of the more recent and promising domains of the application of Metal Organic Frameworks (MOFs) is the biomedical one. To fulfil the keystone requirements of bioapplications, i.e. biosafety and activity, endogenous and/or bioactive motifs (cations, organic ligands or both) have been successfully used as constitutive building blocks to construct Metal Biomolecule Frameworks (also known as bioMOFs). This review highlights the latest advances in 3D bioMOF structures, from their synthesis to their biorelated activities in different biorelated areas including drug delivery, imaging, and sensing, classifying them by the nature of the active component.

6.
J Mater Chem B ; 5(43): 8563-8569, 2017 Nov 21.
Article in English | MEDLINE | ID: mdl-32264524

ABSTRACT

The efficacy of the routinely used anti-HIV (Human Immunodeficiency Virus) therapy based on nucleoside reverse transcriptase inhibitors (NRTIs) is limited by the poor cellular uptake of the active triphosphorylated metabolites and the low efficiency of intracellular phosphorylation of their prodrugs. Nanoparticles of iron(iii) polycarboxylate Metal-Organic Frameworks (nanoMOFs) are promising drug nanocarriers. In this study, two active triphosphorylated NRTIs, azidothymidine triphosphate (AZT-Tp) and lamivudine triphosphate (3TC-Tp), were successfully co-encapsulated into the biocompatible mesoporous iron(iii) trimesate MIL-100(Fe) nanoMOF in order to improve anti-HIV therapies. The drug loaded nanoMOFs could be stored for up to 2-months and reconstituted after freeze drying, retaining similar physicochemical properties. Their antiretroviral activity was evidenced in vitro on monocyte-derived macrophages experimentally infected with HIV, making these co-encapsulated nanosystems excellent HIV-microbicide candidates.

7.
Int J Pharm ; 511(2): 1042-7, 2016 Sep 25.
Article in English | MEDLINE | ID: mdl-27515292

ABSTRACT

Metal-organic frameworks have shown interesting features for biomedical applications, such as drug delivery and imaging agents. The benchmarked mesoporous iron(III) trimesate MIL-100 MOF nanocarrier combines progressive release of high drug cargoes with absence of visible in vivo toxicity. Although in a previous study pharmacokinetics and biodistribution of MIL-100 nanoparticles were evaluated in the long term (from 24h to 1 month), the crucial times for drug targeting and delivery applications are shorter (up to 24h). Thus, this work aims to study the blood circulating profile and organ accumulation of MIL-100 nanocarrier at early times after administration. For this purpose, after intravenous administration to rats, both constitutive components of MIL-100 (trimesate and iron) were quantified by high performance liquid chromatography and a spectrophotometric method, respectively. The pharmacokinetic profile suggested that the nanoparticles act as a depot in the blood stream during the first hours before being cleared. Accumulation took mainly place in the liver and, in some extent, in the spleen. Nevertheless, histological studies demonstrated the absence of morphological alterations due to the presence of the particles in these organs. Liver function was however slightly altered as reflected by the increased plasma aspartate aminotransferase concentrations. Finally trimesate was progressively eliminated in urine.


Subject(s)
Iron Compounds/administration & dosage , Iron Compounds/metabolism , Nanoparticles/administration & dosage , Nanoparticles/metabolism , Administration, Intravenous , Animals , Biological Availability , Female , Rats , Rats, Wistar , Time Factors
8.
J Mater Chem B ; 4(4): 585-588, 2016 Jan 28.
Article in English | MEDLINE | ID: mdl-32262940

ABSTRACT

Nanoparticles of a mesoporous iron(iii) trimesate MIL-100 nanocarrier encapsulating high amounts of the challenging antineoplastic busulfan were administered to rats and compared with the commercial Busilvex®. Large differences in serum concentration of both busulfan and trimesate revealed the great impact of drug encapsulation both on the drug and on nanoparticle pharmacokinetics during the first 24 h of administration.

9.
Dalton Trans ; 44(45): 19687-92, 2015 Dec 07.
Article in English | MEDLINE | ID: mdl-26473182

ABSTRACT

Stability and sorption of Metal-Organic Frameworks (MOFs) towards water are critical in many applications, and can a priori be modulated through the introduction of suitable organic functional groups on their backbone. We report here the preparation of a series of Zr(iv)-based MOFs functionalized with alkyl and perfluoroalkyl groups and their characterization by X-ray powder diffraction, multi-nuclei ((1)H, (13)C, (19)F) solid state nuclear magnetic resonance analyses, and nitrogen sorption measurements at 77 K. Their water sorption behavior was evaluated at 298 K and related to their physico-chemical features, highlighting both the effect of the confinement and the nature of the functional groups on the hydrophilic/hydrophobic balance.

10.
Chem Commun (Camb) ; 51(50): 10194-7, 2015 Jun 25.
Article in English | MEDLINE | ID: mdl-26015999

ABSTRACT

The scalable and environmentally-friendly synthesis of mixed Fe(III)/M(II) (M = Ni, Co, Mg) polycarboxylate porous MOFs based on the Secondary Building Unit approach is reported. A combination of in situ infrared spectroscopy, (57)Fe Mössbauer spectrometry and adsorption microcalorimetry confirms the direct accessibility of the iron(III) and metal(II) sites under low temperature activation conditions.

11.
Sci Rep ; 5: 7925, 2015 Jan 21.
Article in English | MEDLINE | ID: mdl-25603994

ABSTRACT

Nanoparticles made of metal-organic frameworks (nanoMOFs) attract a growing interest in gas storage, separation, catalysis, sensing and more recently, biomedicine. Achieving stable, versatile coatings on highly porous nanoMOFs without altering their ability to adsorb molecules of interest represents today a major challenge. Here we bring the proof of concept that the outer surface of porous nanoMOFs can be specifically functionalized in a rapid, biofriendly and non-covalent manner, leading to stable and versatile coatings. Cyclodextrin molecules bearing strong iron complexing groups (phosphates) were firmly anchored to the nanoMOFs' surface, within only a few minutes, simply by incubation with aqueous nanoMOF suspensions. The coating procedure did not affect the nanoMOF porosity, crystallinity, adsorption and release abilities. The stable cyclodextrin-based coating was further functionalized with: i) targeting moieties to increase the nanoMOF interaction with specific receptors and ii) poly(ethylene glycol) chains to escape the immune system. These results pave the way towards the design of surface-engineered nanoMOFs of interest for applications in the field of targeted drug delivery, catalysis, separation and sensing.


Subject(s)
Coated Materials, Biocompatible/chemistry , Materials Testing , Nanoparticles/chemistry , Animals , Cell Line , Mice , Porosity
12.
Article in English | MEDLINE | ID: mdl-23939202

ABSTRACT

A simple liquid-liquid extraction procedure and quantification by high-performance liquid chromatography (HPLC) method coupled to a diode-array detector (DAD) of genistein (GEN) was developed in various mouse biological matrices. 7-ethoxycoumarin was used as internal standard (IS) and peaks were optimally separated using a Kinetex C18 column (2.6µm, 150mm×2.10mm I.D.) at 40°C with an isocratic elution of mobile phase with sodium dihydrogen phosphate 0.01M in water at pH 2.5 and methanol (55:45, v/v), at a flow rate of 0.25mL/min. The injection volume was 10µL. In all cases, the range of GEN recovery was higher than 61%. The low limit of quantification (LLOQ) was 25ng/mL. The linearity of the calibration curves was satisfactory in all cases as shown by correlation coefficients >0.996. The within-day and between-day precisions were <15% and the accuracy ranged in all cases between 90.14% and 106.05%. This method was successfully applied to quantify GEN in liver, spleen, kidney and plasma after intravenous administration of a single dose (30mg/kg) in female BALB/C mice.


Subject(s)
Chromatography, High Pressure Liquid/methods , Genistein/analysis , Animals , Coumarins/chemistry , Female , Genistein/chemistry , Genistein/isolation & purification , Genistein/pharmacokinetics , Least-Squares Analysis , Liquid-Liquid Extraction , Mice , Mice, Inbred BALB C , Reproducibility of Results , Sensitivity and Specificity , Tissue Distribution
13.
J Mater Chem B ; 1(8): 1101-1108, 2013 Feb 28.
Article in English | MEDLINE | ID: mdl-32260833

ABSTRACT

The encapsulation of two different bioactive molecules, the cosmetic caffeine and the analgesic and anti-inflammatory ibuprofen, has been evaluated by combining impregnation and advanced characterization experimental tools in a series of microporous rigid zirconium(iv) terephthalates UiO-66 bearing different polar or apolar functional groups (-H, -Br, -NH2, -2OH, -NO2, -Cl, -2CF3, -CH3, -2CH3). It has been first evidenced that these hybrid solids exhibit drug payloads that significantly outperform those obtained using current drug formulations or other conventional porous solids. A quantitative structure-activity relationship strategy has been further conducted with the aim of rationalizing the experimental drug uptakes and further emphasizing the most relevant chemical and structural features that significantly impact their encapsulation performances. Indeed, it appears that the caffeine loading is optimized when the functionalized organic linker both shows a large octanol-water partition coefficient and contains grafted functions with low hydrogen bond acceptor abilities, whereas the ibuprofen entrapping is enhanced when the organic linker contains functional groups with a large solvent surface area and free volume, and to a lesser extent low hydrogen bond acceptor abilities. Moreover, it has been shown that the solvent used as media for the biomolecule impregnation plays a crucial role in the encapsulation performance due to the formation of a competitive adsorption process between the solvent and the active molecule.

14.
Nanomedicine (Lond) ; 6(10): 1683-95, 2011 Dec.
Article in English | MEDLINE | ID: mdl-22122581

ABSTRACT

Busulfan is an alkylating agent widely used in chemotherapy, but with severe side effects. Many attempts have been made to entrap busulfan in nanocarriers to avoid liver accumulation and to protect it against rapid degradation in aqueous media. However, poor loadings (≤ 5 wt%) and fast release were generally obtained due to the low affinity of busulfan towards the nanocarriers. Moreover, drug crystallization often occurred during nanoparticle preparation. To circumvent these drawbacks, metal organic framework (MOF) nanoparticles, based on crystalline porous iron (III) carboxylates, have shown an unprecedented loading (up to 25 wt%) of busulfan. This was attributed to the high porosity of nanoMOFs as well as to their hydrophilic-hydrophobic internal microenvironment well adapted to the amphiphilic character of busulfan. NanoMOFs formulations have kept busulfan in molecular form, preventing its crystallization and degradation. Indeed, busulfan was released intact, as proved by the maintenance of its pharmacological activity.


Subject(s)
Busulfan/chemistry , Drug Carriers/chemistry , Nanoparticles/chemistry , Organometallic Compounds/chemistry , Busulfan/pharmacology , Cell Line , Cell Survival/drug effects , Drug Carriers/chemical synthesis , Humans , Hydrophobic and Hydrophilic Interactions , Magnetic Resonance Spectroscopy/methods , Nanoparticles/ultrastructure , Organometallic Compounds/chemical synthesis , Pharmaceutical Preparations/chemistry , Porosity
15.
J Am Chem Soc ; 131(36): 13002-8, 2009 Sep 16.
Article in English | MEDLINE | ID: mdl-19697934

ABSTRACT

This investigation is based on a combination of experimental tools completed by a computational approach to deeply characterize the unusual adsorption behavior of the flexible MIL-53(Fe) in the presence of short linear alkanes. In contrast to the aluminum or chromium analogues we previously reported, the iron MIL-53 solid, which initially exhibits a closed structure in the dry state, shows more complex adsorption isotherms with multisteps occurring at pressures that depend on the nature of the alkane. This behavior has been attributed to the existence of four discrete pore openings during the whole adsorption process. Molecular simulations coupled with in situ X-ray powder diffraction were able to uncover these various structural states.

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