In vitro biocompatibility of mesoporous metal (III; Fe, Al, Cr) trimesate MOF nanocarriers.

The high porosity and versatile composition of the benchmarked mesoporous metal (Fe, Al, Cr) trimesate metal-organic frameworks (MIL-100(Fe, Al, Cr)) make them very promising solids in different strategic industrial and societal domains (separation, catalysis, biomedicine, etc.). In particular, MIL-100(Fe) nanoparticles (NPs) have been recently revealed to be one of the most promising and innovative next generation tools enabling multidrug delivery to overcome cancer resistance. Here, we analyzed the in vitro toxicity of the potential drug nanocarrier MIL-100(Fe) NPs and the effect of the constitutive cation by comparing its cytotoxicity with that one of its Cr and Al analogue NPs. Lung (A549 and Calu-3) and hepatic (HepG2 and Hep3B) cell lines were selected considering pulmonary, ingestion or intravenous exposure modes. First, the complete physicochemical characterization (structural, chemical and colloidal stability) of the MIL-100(Fe, Al, Cr) NPs was performed in the cell culture media. Then, their cytotoxicity was evaluated in the four selected cell lines using a combination of methods from cell impedance, cell survival/death and ROS generation to DNA damage for measuring genotoxicity. Thus, MIL-100(Fe, Al, Cr) NPs did not induce in vitro cell toxicity, even at high doses in the p53 wild type cell lines (A549 and calu-3 (lung) and HepG2 (liver)). The only toxic effect of MIL100-Fe was observed in the hepatocarcinoma cell line Hep3B, which is stress sensitive because it does not express TP53, the guardian of the genome.

[1]  K. Temst,et al.  Selective removal of N-heterocyclic aromatic contaminants from fuels by lewis acidic metal-organic frameworks. , 2011, Angewandte Chemie.

[2]  A. Nakamura,et al.  Recent developments in the use of γ -H2AX as a quantitative DNA double-strand break biomarker , 2011, Aging.

[3]  Leaf Huang,et al.  Intelligent design of multifunctional lipid-coated nanoparticle platforms for cancer therapy. , 2012, Therapeutic delivery.

[4]  Xiu‐Ping Yan,et al.  Metal-organic framework MIL-101 for high-resolution gas-chromatographic separation of xylene isomers and ethylbenzene. , 2010, Angewandte Chemie.

[5]  C. Serre,et al.  Porous metal organic framework nanoparticles to address the challenges related to busulfan encapsulation. , 2011, Nanomedicine.

[6]  M. Allendorf,et al.  Luminescent metal-organic frameworks. , 2009, Chemical Society reviews.

[7]  Christian Serre,et al.  Rationale of Drug Encapsulation and Release from Biocompatible Porous Metal−Organic Frameworks , 2013 .

[8]  J. Lee,et al.  Energy‐Efficient Dehumidification over Hierachically Porous Metal–Organic Frameworks as Advanced Water Adsorbents , 2012, Advanced materials.

[9]  James H. Adair,et al.  Nanoparticulate alternatives for drug delivery. , 2010, ACS nano.

[10]  J. Harvey,et al.  Genotoxicity screening via the γH2AX by flow assay. , 2011, Mutation research.

[11]  C. Serre,et al.  A biocompatible porous Mg-gallate metal-organic framework as an antioxidant carrier. , 2015, Chemical communications.

[12]  S. Doak,et al.  NanoGenotoxicology: the DNA damaging potential of engineered nanomaterials. , 2009, Biomaterials.

[13]  E. Fattal,et al.  Nanomedicine technology: current achievements and new trends , 2014, Clinical and Translational Imaging.

[14]  S. Qiu,et al.  Metal-organic framework membranes: from synthesis to separation application. , 2014, Chemical Society reviews.

[15]  Chad A Mirkin,et al.  Nucleic acid-metal organic framework (MOF) nanoparticle conjugates. , 2014, Journal of the American Chemical Society.

[16]  Demin Liu,et al.  Nanoscale metal-organic frameworks for biomedical imaging and drug delivery. , 2011, Accounts of chemical research.

[17]  M. Burghammer,et al.  Synthesis, Single-Crystal X-ray Microdiffraction, and NMR Characterizations of the Giant Pore Metal-Organic Framework Aluminum Trimesate MIL-100 , 2009 .

[18]  X. López,et al.  Pro-oxidant activity of aluminum: stabilization of the aluminum superoxide radical ion. , 2011, The journal of physical chemistry. A.

[19]  A. Slawin,et al.  Synthesis, characterisation and adsorption properties of microporous scandium carboxylates with rigid and flexible frameworks , 2011 .

[20]  V. Paget,et al.  Human cell line-dependent WC-Co nanoparticle cytotoxicity and genotoxicity: a key role of ROS production. , 2015, Toxicological sciences : an official journal of the Society of Toxicology.

[21]  G. Czapski,et al.  Unusual copper-induced sensitization of the biological damage due to superoxide radicals. , 1981, The Journal of biological chemistry.

[22]  Omid C Farokhzad,et al.  Insight into nanoparticle cellular uptake and intracellular targeting. , 2014, Journal of controlled release : official journal of the Controlled Release Society.

[23]  Qiang Xu,et al.  Metal-organic framework composites. , 2014, Chemical Society reviews.

[24]  Gérard Férey,et al.  Metal-organic frameworks in biomedicine. , 2012, Chemical reviews.

[25]  Vicki Stone,et al.  Efficacy of Simple Short-Term in Vitro Assays for Predicting the Potential of Metal Oxide Nanoparticles to Cause Pulmonary Inflammation , 2008, Environmental health perspectives.

[26]  L. Helm,et al.  Inorganic and bioinorganic solvent exchange mechanisms. , 2005, Chemical reviews.

[27]  Fernando Rodrigues-Lima,et al.  Nanoparticles: molecular targets and cell signalling , 2011, Archives of Toxicology.

[28]  C. Serre,et al.  Cytotoxicity of nanoscaled metal-organic frameworks. , 2014, Journal of materials chemistry. B.

[29]  P Bergonzo,et al.  Carboxylated nanodiamonds are neither cytotoxic nor genotoxic on liver, kidney, intestine and lung human cell lines , 2014, Nanotoxicology.

[30]  Samir Mitragotri,et al.  Control of endothelial targeting and intracellular delivery of therapeutic enzymes by modulating the size and shape of ICAM-1-targeted carriers. , 2008, Molecular therapy : the journal of the American Society of Gene Therapy.

[31]  H. Zhou,et al.  Metal-organic frameworks (MOFs). , 2014, Chemical Society reviews.

[32]  Gérard Férey,et al.  Hydrogen storage in the giant-pore metal-organic frameworks MIL-100 and MIL-101. , 2006, Angewandte Chemie.

[33]  Gérard Férey,et al.  Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging. , 2010, Nature materials.

[34]  Young Kwan Park,et al.  Crystal structure and guest uptake of a mesoporous metal-organic framework containing cages of 3.9 and 4.7 nm in diameter. , 2007, Angewandte Chemie.

[35]  C. Serre,et al.  MOFs in Pharmaceutical Technology , 2014 .

[36]  Yolanda Diebold,et al.  Applications of nanoparticles in ophthalmology , 2010, Progress in Retinal and Eye Research.

[37]  C. Serre,et al.  Investigation of acid sites in a zeotypic giant pores chromium(III) carboxylate. , 2006, Journal of the American Chemical Society.

[38]  Mohamed Eddaoudi,et al.  A supermolecular building approach for the design and construction of metal-organic frameworks. , 2014, Chemical Society reviews.

[39]  A. Hartwig,et al.  Carcinogenic metal compounds: recent insight into molecular and cellular mechanisms , 2008, Archives of Toxicology.

[40]  Luís D. Carlos,et al.  Luminescent multifunctional lanthanides-based metal-organic frameworks. , 2011, Chemical Society reviews.

[41]  Demin Liu,et al.  Nanoscale Metal–Organic Frameworks for the Co-Delivery of Cisplatin and Pooled siRNAs to Enhance Therapeutic Efficacy in Drug-Resistant Ovarian Cancer Cells , 2014, Journal of the American Chemical Society.

[42]  Scott E McNeil,et al.  Nanomaterial standards for efficacy and toxicity assessment. , 2010, Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology.

[43]  Rafael Núñez,et al.  DNA measurement and cell cycle analysis by flow cytometry. , 2001, Current issues in molecular biology.

[44]  S. Jackson,et al.  Regulation of p53 in response to DNA damage , 1999, Oncogene.

[45]  Debasis Bagchi,et al.  Chromium (VI)‐induced oxidative stress, apoptotic cell death and modulation of p53 tumor suppressor gene , 2001, Molecular and Cellular Biochemistry.

[46]  Seth M. Cohen,et al.  Postsynthetic modification of metal-organic frameworks. , 2009, Chemical Society reviews.

[47]  M. V. Lozano,et al.  Heparin‐Engineered Mesoporous Iron Metal‐Organic Framework Nanoparticles: Toward Stealth Drug Nanocarriers , 2015, Advanced healthcare materials.

[48]  Fernando Rodrigues-Lima,et al.  Intracellular signal modulation by nanomaterials. , 2014, Advances in experimental medicine and biology.

[49]  Thu-Hoa Tran-Thi,et al.  Optical chemical sensors based on hybrid organic-inorganic sol-gel nanoreactors. , 2011, Chemical Society reviews.

[50]  Ruxandra Gref,et al.  In depth analysis of the in vivo toxicity of nanoparticles of porous iron(III) metal–organic frameworks , 2013 .

[51]  J. Lee,et al.  MIL-100(V) – A mesoporous vanadium metal organic framework with accessible metal sites , 2012 .

[52]  Qiang Zhang,et al.  Tuning the structure and function of metal-organic frameworks via linker design. , 2014, Chemical Society reviews.

[53]  K. Donaldson,et al.  Principal component and causal analysis of structural and acute in vitro toxicity data for nanoparticles , 2014, Nanotoxicology.

[54]  C. Serre,et al.  Controlled reducibility of a metal-organic framework with coordinatively unsaturated sites for preferential gas sorption. , 2010, Angewandte Chemie.

[55]  M. J. Santander-Ortega,et al.  Understanding the colloidal stability of the mesoporous MIL-100(Fe) nanoparticles in physiological media. , 2014, Langmuir : the ACS journal of surfaces and colloids.

[56]  V. Paget,et al.  Toxicity and genotoxicity of nano-SiO2 on human epithelial intestinal HT-29 cell line. , 2012, The Annals of occupational hygiene.

[57]  Omar K Farha,et al.  Metal-organic framework materials as catalysts. , 2009, Chemical Society reviews.

[58]  M. Grinstaff,et al.  Biocompatible and bioactive surface modifications for prolonged in vivo efficacy. , 2012, Chemical reviews.

[59]  Ghislaine Lacroix,et al.  Specific Uptake and Genotoxicity Induced by Polystyrene Nanobeads with Distinct Surface Chemistry on Human Lung Epithelial Cells and Macrophages , 2015, PloS one.

[60]  Ana E. Platero‐Prats,et al.  Green Microwave Synthesis of MIL‐100(Al, Cr, Fe) Nanoparticles for Thin‐Film Elaboration , 2012 .

[61]  Eleonore Fröhlich,et al.  The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles , 2012, International journal of nanomedicine.

[62]  Julia Gorelik,et al.  Respiratory epithelial cytotoxicity and membrane damage (holes) caused by amine-modified nanoparticles , 2012, Nanotoxicology.

[63]  C. Serre,et al.  High uptakes of CO2 and CH4 in mesoporous metal-organic frameworks MIL-100 and MIL-101. , 2008, Langmuir : the ACS journal of surfaces and colloids.

[64]  A. Bird,et al.  Metal-Responsive Transcription Factors That Regulate Iron, Zinc, and Copper Homeostasis in Eukaryotic Cells , 2004, Eukaryotic Cell.

[65]  Gérard Férey,et al.  A hybrid solid with giant pores prepared by a combination of targeted chemistry, simulation, and powder diffraction. , 2004, Angewandte Chemie.

[66]  Li Zhang,et al.  Applications of metal-organic frameworks in heterogeneous supramolecular catalysis. , 2014, Chemical Society reviews.

[67]  Tracy K. Pettinger,et al.  Nanopharmaceuticals (part 1): products on the market , 2014, International journal of nanomedicine.

[68]  Katharina Landfester,et al.  Amino‐functionalized polystyrene nanoparticles activate the NLRP3 inflammasome in human macrophages , 2011, ACS nano.

[69]  Jae-Min Oh,et al.  Integrated bio-inorganic hybrid systems for nano-forensics. , 2011, Chemical Society reviews.

[70]  Yanfeng Yue,et al.  Luminescent functional metal-organic frameworks. , 2012, Chemical Reviews.

[71]  M. Ferrari Cancer nanotechnology: opportunities and challenges , 2005, Nature Reviews Cancer.

[72]  W. Boyes,et al.  Detection of TiO2 nanoparticles in cells by flow cytometry , 2010, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[73]  H. Fenton,et al.  LXXIII.—Oxidation of tartaric acid in presence of iron , 1894 .

[74]  Stephanie E. A. Gratton,et al.  The effect of particle design on cellular internalization pathways , 2008, Proceedings of the National Academy of Sciences.

[75]  C. Serre,et al.  Synthesis and catalytic properties of MIL-100(Fe), an iron(III) carboxylate with large pores. , 2007, Chemical communications.

[76]  P. Couvreur,et al.  Quantification of fumaric acid in liver, spleen and urine by high-performance liquid chromatography coupled to photodiode-array detection. , 2011, Journal of pharmaceutical and biomedical analysis.

[77]  Jing Li,et al.  Luminescent metal-organic frameworks for chemical sensing and explosive detection. , 2014, Chemical Society reviews.

[78]  R. Corriu,et al.  From molecular chemistry to hybrid nanomaterials. Design and functionalization. , 2011, Chemical Society reviews.

[79]  Christopher Exley,et al.  The immunobiology of aluminium adjuvants: how do they really work? , 2010, Trends in immunology.

[80]  Jörg Huwyler,et al.  Nanomedicine in cancer therapy: challenges, opportunities, and clinical applications. , 2015, Journal of controlled release : official journal of the Controlled Release Society.

[81]  Gérard Férey,et al.  Metal-organic frameworks as efficient materials for drug delivery. , 2006, Angewandte Chemie.

[82]  Jihyun An,et al.  Metal-biomolecule frameworks (MBioFs). , 2011, Chemical communications.

[83]  N. Roher,et al.  Synthesis, culture medium stability, and in vitro and in vivo zebrafish embryo toxicity of metal-organic framework nanoparticles. , 2015, Chemistry.