Publications by authors named "Lamiaa M A Ali"

17 Publications

  • Page 1 of 1

A rational study of the influence of Mn-insertion in Prussian blue nanoparticles on their photothermal properties.

J Mater Chem B 2021 Nov 2. Epub 2021 Nov 2.

IBMM, Univ. Montpellier, CNRS, ENSCM, Montpellier, France.

We investigated a series of Mn-Prussian blue (PB) nanoparticles NaMnFe[Fe(CN)]·HO of similar size, surface state and cubic morphology with various amounts of Mn synthesized through a one step self-assembly reaction. We demonstrated by a combined experimental-theoretical approach that during the synthesis, Mn substituted Fe up to a Mn/Na-Mn-Fe ratio of 32 at% in the PB structure, while for higher amounts, the Mn[Fe(CN)] analogue is obtained. For comparison, the post-synthetic insertion of Mn2+ in PB nanoparticles was also investigated and completed with Monte-Carlo simulations to probe the plausible adsorption sites. The photothermal conversion efficiency () of selected samples was determined and showed a clear dependence on the Mnamount with a maximum efficiency for a Mn/Na-Mn-Fe ratio of 10 at% associated with a dependence on the nanoparticle concentration. Evaluation of the photothermal properties of these nanoparticles performed on triple negative human breast adenocarcinoma (MDA-MB-231) cells by using continuous and pulsed laser irradiation confirm their excellent PTT efficiency permitting low dose use.
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http://dx.doi.org/10.1039/d1tb00888aDOI Listing
November 2021

Modified Indulines: From Dyestuffs to Theranostic Agents.

ACS Appl Mater Interfaces 2021 Jul 23;13(26):30337-30349. Epub 2021 Jun 23.

Aix Marseille Université, CNRS, CINaM, UMR 7325, Campus de Luminy, 13288 Marseille Cedex 09, France.

The efficient, versatile, and straightforward synthesis of the first -alkyl analogues of induline 3B ( and ) is reported. Thanks to the introduction of lipophilic substituents and their attractive photophysical properties (far-red emission and production of singlet oxygen), phenazinium can be used as a theranostic agent and shows, at very low concentrations (100 nM), a remarkable ability to (i) image cells and zebrafish embryos with high quality under both mono- (514 nm) and biphotonic (790 and 810 nm) excitations, (ii) efficiently and quickly penetrate cancer cells rather than healthy fibroblasts, and (iii) induce a total or almost total cancer cell death and after illumination (λ = 540-560 nm). The molecular structure of is based on a triamino-phenazinium core only, with no need for additional components, highlighting the emergence of a minimalistic and versatile class of fluorescent probes for targeted photodynamic cancer therapy.
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http://dx.doi.org/10.1021/acsami.1c05933DOI Listing
July 2021

Periodic Mesoporous Ionosilica Nanoparticles for Green Light Photodynamic Therapy and Photochemical Internalization of siRNA.

ACS Appl Mater Interfaces 2021 Jun 17;13(25):29325-29339. Epub 2021 Jun 17.

IBMM, Univ. Montpellier, CNRS, ENSCM; Avenue Charles Flahault, CEDEX 05, 34093 Montpellier, France.

We report periodic mesoporous ionosilica nanoparticles (PMINPs) as versatile nano-objects for imaging, photodynamic therapy (PDT), and efficient adsorption and delivery of small interfering RNA (siRNA) into breast cancer cells. In order to endow these nanoparticles with PDT and siRNA photochemical internalization (PCI) properties, a porphyrin derivative was integrated into the ionosilica framework. For this purpose, we synthesized PMINPs hydrolysis-cocondensation procedures from oligosilylated ammonium and porphyrin precursors. The formation of these nano-objects was proved by transmission electron microscopy. The formed nanoparticles were then thoroughly characterized solid-state NMR, nitrogen sorption, dynamic light scattering, and UV-vis and fluorescence spectroscopies. Our results indicate the formation of highly porous nanorods with a length of 108 ± 9 nm and a width of 54 ± 4 nm. A significant PDT effect of type I mechanism (95 ± 2.8% of cell death) was observed upon green light irradiation in nanoparticle-treated breast cancer cells, while the blue light irradiation caused a significant phototoxic effect in non-treated cells. Furthermore, PMINPs formed stable complexes with siRNA (up to 24 h), which were efficiently internalized into the cells after 4 h of incubation mostly with the energy-dependent endocytosis process. The PCI effect was obvious with green light irradiation and successfully led to 83 ± 1.1% silencing of the luciferase gene in luciferase-expressing breast cancer cells, while no gene silencing effect was observed with blue light irradiation. The present work highlights the high potential of porphyrin-doped PMINPs as multifunctional nanocarriers for nucleic acids, such as siRNA, with a triple ability to perform imaging, PDT, and PCI.
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http://dx.doi.org/10.1021/acsami.1c05848DOI Listing
June 2021

Mesoporous silica adsorbents modified with amino polycarboxylate ligands - functional characteristics, health and environmental effects.

J Hazard Mater 2021 03 2;406:124698. Epub 2020 Dec 2.

ICGM, Univ. Montpellier, CNRS, ENSCM, Case 1701, Place Eugène Bataillon, CEDEX 05, 34095 Montpellier, France. Electronic address:

A series of hybrid adsorbents were produced by surface modification with amino polycarboxylate ligands of industrially available microparticles (MP) of Kromasil® mesoporous nanostructured silica beads, bearing grafted amino propyl ligands. Produced materials, bearing covalently bonded functions as EDTA and TTHA, original Kromasil®, bearing amino propyl ligands, and bare particles, obtained by thermal treatment of Kromasil® in air, were characterized by SEM-EDS, AFM, FTIR, TGA and gas sorption techniques. Adsorption kinetics and capacity of surface-modified particles to adsorb Rare Earth Elements (REE), crucial for extraction in recycling processes, were evaluated under dynamic conditions, revealing specificity matching the ligand nature and the size of REE cations. A detailed comparison with earlier reported adsorbents for REE extraction was presented. The cytotoxicity was assessed using four different types of healthy cells, human skeletal muscles derived cells (SKMDC), fibroblast cells, macrophage cells (RAW264.7), and human umbilical vein endothelial cells (HUVECs), indicating lower toxicity of ligand-free MP than MP bearing amino poly-carboxylate functions. Internalization of the MP inside the cells and release of nitric oxide were observed. In addition, zebrafish embryos were exposed to high concentrations of MP and did not show any pronounced toxicity.
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http://dx.doi.org/10.1016/j.jhazmat.2020.124698DOI Listing
March 2021

Cell-Selective siRNA Delivery Using Glycosylated Dynamic Covalent Polymers Self-Assembled In Situ by RNA Templating.

Angew Chem Int Ed Engl 2021 03 28;60(11):5783-5787. Epub 2021 Jan 28.

Institut des Biomolécules Max Mousseron (IBMM), CNRS, Université de Montpellier, ENSCM, Montpellier, France.

Dynamic covalent libraries enable exploring complex chemical systems from which bioactive assemblies can adaptively emerge through template effects. In this work, we studied dynamic covalent libraries made of complementary bifunctional cationic peptides, yielding a diversity of species from macrocycles to polymers. Although polymers are typically expressed only at high concentration, we found that siRNA acts as a template in the formation of dynamic covalent polymers at low concentration in a process guided by electrostatic binding. Using a glycosylated building block, we were able to show that this templated polymerization further translates into the multivalent presentation of carbohydrate ligands, which subsequently promotes cell uptake and even cell-selective siRNA delivery.
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http://dx.doi.org/10.1002/anie.202014066DOI Listing
March 2021

Hydrocarbon-Stapled Peptide Based-Nanoparticles for siRNA Delivery.

Nanomaterials (Basel) 2020 Nov 25;10(12). Epub 2020 Nov 25.

IBMM, Univ Montpellier, CNRS, ENSCM, 34093 Montpellier, France.

Small interfering RNAs (siRNAs) are promising molecules for developing new therapies based on gene silencing; however, their delivery into cells remains an issue. In this study, we took advantage of stapled peptide technology that has emerged as a valuable strategy to render natural peptides more structured, resistant to protease degradation and more bioavailable, to develop short carriers for siRNA delivery. From the pool of stapled peptides that we have designed and synthesized, we identified non-toxic vectors that were able to efficiently encapsulate siRNA, transport them into the cell and induce gene silencing. Remarkably, the most efficient stapled peptide (JMV6582), is composed of only eight amino-acids and contains only two cationic charges.
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http://dx.doi.org/10.3390/nano10122334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760004PMC
November 2020

Two-Photon Absorbing AIEgens: Influence of Stereoconfiguration on Their Crystallinity and Spectroscopic Properties and Applications in Bioimaging.

ACS Appl Mater Interfaces 2020 Dec 20;12(49):55157-55168. Epub 2020 Nov 20.

Univ. Lyon, ENS Lyon, CNRS, Université Lyon 1, Laboratoire de Chimie, UMR 5182, 46 Allée d'Italie, 69364 Lyon, France.

This paper aims at designing chromophores with efficient aggregation-induced emission (AIE) properties for two-photon fluorescence microscopy (2PFM), which is one of the best-suited types of microscopy for the imaging of living organisms or thick biological tissues. Tetraphenylethylene (TPE) derivatives are common building blocks in the design of chromophores with efficient AIE properties. Therefore, in this study, extended TPE AIEgens specifically optimized for two-photon absorption (2PA) are synthesized and the resulting (/) isomers are separated using chromatography on chiral supports. Comparative characterization of the AIE properties is performed on the pure () and () isomers and the mixture, allowing us, in combination with powder X-ray diffraction and solid-state NMR, to document a profound impact of crystallinity on solid-state fluorescence properties. In particular, we show that stereopure AIEgens form aggregates of superior crystallinity, which in turn exhibit a higher fluorescence quantum yield compared to diastereoisomers mixtures. Preparation of stereopure organic nanoparticles affords very bright fluorescent contrast agents, which are then used for cellular and intravital two-photon microscopy on human breast cancer cells and on zebrafish embryos.
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http://dx.doi.org/10.1021/acsami.0c15810DOI Listing
December 2020

Biological Assessment of Laser-Synthesized Silicon Nanoparticles Effect in Two-Photon Photodynamic Therapy on Breast Cancer MCF-7 Cells.

Nanomaterials (Basel) 2020 Jul 26;10(8). Epub 2020 Jul 26.

IBMM, Univ Montpellier, CNRS, ENSCM, 34093 Montpellier, France.

Driven by their distinctive physiological activities, biological properties and unique theranostic modalities, silicon nanoparticles (SiNPs) are one of the promising materials for the development of novel multifunctional nanoplatforms for biomedical applications. In this work, we assessed the possibility to use laser-synthesized Si NPs as photosensitizers in two-photon excited photodynamic therapy (TPE-PDT) modality. Herein, we used an easy strategy to synthesize ultraclean and monodispersed SiNPs using laser ablation and fragmentation sequences of silicon wafer in aqueous solution, which prevent any specific purification step. Structural analysis revealed the spherical shape of the nanoparticles with a narrow size distribution centered at the mean size diameter of 62 nm ± 0.42 nm, while the negative surface charge of -40 ± 0.3 mV ensured a great stability without sedimentation over a long period of time. In vitro studies on human cancer cell lines (breast and liver) and healthy cells revealed their low cytotoxicity without any light stimulus and their therapeutic potential under TPE-PDT mode at 900 nm with a promising cell death of 45% in case of MCF-7 breast cancer cells, as a consequence of intracellular reactive oxygen species release. Their luminescence emission inside the cells was clearly observed at UV-Vis region. Compared to Si nanoparticles synthesized via chemical routes, which are often linked to additional modules with photochemical and photobiological properties to boost photodynamic effect, laser-synthesized SiNPs exhibit promising intrinsic therapeutic and imaging properties to develop advanced strategy in nanomedicine field.
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http://dx.doi.org/10.3390/nano10081462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466460PMC
July 2020

Imidazopyridine-fused [1,3]diazepinones: modulations of positions 2 to 4 and their impacts on the anti-melanoma activity.

J Enzyme Inhib Med Chem 2020 Dec;35(1):935-949

Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Universités Montpellier, UFR des Sciences Pharmaceutiques et Biologiques, Montpellier, France.

A series of 19 novel pyrido-imidazodiazepinones, with modulations of positions 2, 3 and 4 of the diazepine ring were synthesised and screened for their cytotoxic activities against two melanoma cell lines (A375 and MDA-MB-435) and for their potential toxicity against NIH-3T3 non-cancerous cells. Selected compounds were also evaluated on the NCI-60 cell line panel. The SAR study revealed that the molecular volume and the LogP of compounds modified at position 2 were significantly correlated with the activity of these compounds on melanoma cell lines. Moreover, introduction of a heterocyclic group at position 2 or an azido-alkyl chain at position 4 led to compounds displaying a significantly different activity profile on the NCI-60 cell line panel, compared to phenyl-substituted compounds at position 2 of the diazepinone. This study provides us crucial information for the development of new derivatives active against melanoma.
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http://dx.doi.org/10.1080/14756366.2020.1748024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7170309PMC
December 2020

Effect of superparamagnetic iron oxide nanoparticles on glucose homeostasis on type 2 diabetes experimental model.

Life Sci 2020 Mar 27;245:117361. Epub 2020 Jan 27.

Department of Biochemistry, Medical Research Institute, University of Alexandria, Alexandria, Egypt.

Aims: Evaluation of the anti-diabetic effect of superparamagnetic iron oxide nanoparticles (SPIONs) on Type 2 diabetic rats and compared their effect to metformin treatment.

Main Methods: Diabetic rats were treated with different doses of nanoparticles one time per week for 4 weeks. Fasting blood glucose level was determined for studied groups during the experimental period (30 days). At the end of the experiment, oral glucose tolerance test was carried out, serum samples were collected for biochemical assays. Then animals were sacrificed to obtain tissues for assessment of glucose transporters, insulin receptors and insulin signaling proteins.

Key Finding: SPIONs treatment normalized fasting blood glucose and lowering insulin level in diabetic rats compared to untreated diabetic rats. SPIONs significantly ameliorate the glucose sensing and the active components of insulin signaling pathway. The anti-diabetic effects of SPIONs may be mediated through its effect on (i) hepatic peroxisome proliferator-activated receptor gamma coactivator 1-alpha content, which induced by SPIONs treatment in a dose-dependent manner, (ii) adipocytokines as SPIONs treated diabetic rats showed significantly higher levels of adiponectin and lower retinol binding protein 4 compared to untreated diabetic rats, (iii) lipid profile as SPIONs treatment significantly corrected the lipid profile in a dose-dependent manner and to a similar extent as metformin or even better.

Significance: To our knowledge, this is the first study that explores the anti-diabetic effects of SPIONs on diabetic model.
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http://dx.doi.org/10.1016/j.lfs.2020.117361DOI Listing
March 2020

Encapsulation of Upconversion Nanoparticles in Periodic Mesoporous Organosilicas.

Molecules 2019 Nov 9;24(22). Epub 2019 Nov 9.

Institut Charles Gerhardt Montpellier, case 1701, UMR5253, CNRS-UM-ENSCM, Place Eugène Bataillon, 34095 Montpellier, CEDEX 05, France.

(1) Background: Nanomedicine has recently emerged as a promising field, particularly for cancer theranostics. In this context, nanoparticles designed for imaging and therapeutic applications are of interest. We, therefore, studied the encapsulation of upconverting nanoparticles in mesoporous organosilica nanoparticles. Indeed, mesoporous organosilica nanoparticles have been shown to be very efficient for drug delivery, and upconverting nanoparticles are interesting for near-infrared and X-ray computed tomography imaging, depending on the matrix used. (2) Methods: Two different upconverting-based nanoparticles were synthesized with Yb-Er as the upconverting system and NaYF or BaLuF as the matrix. The encapsulation of these nanoparticles was studied through the sol-gel procedure with bis(triethoxysilyl)ethylene and bis(triethoxysilyl)ethane in the presence of CTAB. (3) Results: with bis(triethoxysilyl)ethylene, BaLuF: Yb-Er, nanoparticles were not encapsulated, but anchored on the surface of the obtained mesoporous nanorods BaLuF: [email protected] With bis(triethoxysilyl)ethane, BaLuF: Yb-Er and NaYF: Yb-Ernanoparticles were encapsulated in the mesoporous cubic structure leading to BaLuF: [email protected] and NaYF: [email protected], respectively. (4) Conclusions: upconversion nanoparticles were located on the surface of mesoporous nanorods obtained by hydrolysis polycondensation of bis(triethoxysilyl)ethylene, whereas encapsulation occurred with bis(triethoxysilyl)ethane. The later nanoparticles NaYF: [email protected] or BaLuF: [email protected] were promising for applications with cancer cell imaging or X-ray-computed tomography respectively.
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http://dx.doi.org/10.3390/molecules24224054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891486PMC
November 2019

Topological Requirements for CI-M6PR-Mediated Cell Uptake.

Bioconjug Chem 2019 10 26;30(10):2533-2538. Epub 2019 Sep 26.

Institut des Biomolécules Max Mousseron , UMR CNRS-UM-ENSCM 5247, UFR des Sciences Pharmaceutiques et Biologiques, 15 Avenue Charles Flahault , 34093 Montpellier Cedex 5, France.

The 300 kDa cation-independent M6P receptor (CI-MPR) mediates ligand internalization and trafficking to the endolysosomal compartments. Because of its endocytotic nature, it has been recognized as a promising class of receptors for target component delivery. Its cellular uptake involves the simultaneous binding of two protein units resulting in the formation of receptor dimers. While many multivalent glycoconjugates have been reported to date, little is known about the topological requests to induce an effective recruitment of CI-MPRs. We herein describe the synthesis and cell uptake ability of a set of highly organized glycoclusters bearing one to three saccharide units. The spatial arrangement of carbohydrate ligands is ensured by a heterocyclic γ-peptide central core.
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http://dx.doi.org/10.1021/acs.bioconjchem.9b00590DOI Listing
October 2019

Synthesis and Anticancer Activity of Gold Porphyrin Linked to Malonate Diamine Platinum Complexes.

Inorg Chem 2019 Sep 5;58(18):12395-12406. Epub 2019 Sep 5.

CEISAM, Chimie Et Interdisciplinarité, Synthèse, Analyse, Modélisation, CNRS, UMR CNRS 6230 , Université LUNAM, Université de Nantes, UFR des Sciences et des Techniques , 2, rue de la Houssinière , BP 92208, 44322 Nantes Cedex 3, France.

Recently, gold(III) porphyrins have gained great interest as anticancer drugs not only for the stability of gold(III) but also for the functionalization of the porphyrin to allow bridging with another metal such as platinum(II). We report here, for the first time, the synthesis of three new bimetal compounds containing a gold(III) porphyrin conjugated to a platinum diamine moiety through malonate bridging to obtain enhanced cytotoxicity from both metals combined with the phototoxicity of the porphyrin. The three complexes differ in the type of diamine ligand around platinum(II): ammonia (NH), cyclohexanediamine (CyDA), and pyridylmethylamine (Py). The synthesis was carried out using the complexation of activated malonic acid derivatives with aquadiaminoplatinum(II) complexes, and the products were characterized by IR, NMR, mass spectra, and elementary analysis. The cytotoxic activity of the conjugates was screened in both healthy cell lines and cancer cell lines, human fibroblast cells (FS-68) and human breast cancer cells (MCF-7), and was compared to that of the corresponding platinum(II) complexes. The cyclohexyldiamine (CyDA) derivative exhibited the greatest cytotoxic effect among the series. The results showed that Au(III)/Pt(II) conjugates are more potent by 2-5.6-fold than the corresponding platinum complexes. Moreover, the dyad AuP-PtCyDA is 18% more potent and also more selective toward cancer cells than the parent gold porphyrin substituted with malonic acid. On the other hand, the IC of the dyad AuP-PtCyDA is 43% lower than that of AuTPP but is more selective toward healthy cells. Singlet oxygen measurements indicated that gold(III) porphyrin derivatives are poor oxygen sensitizers and cell death occurred potentially due to generation of other reactive oxygen species (ROS) upon reductive quenching of the gold porphyrin excited state. In addition, the increase in cancer cell death obtained after light irradiation is totally absent in healthy cells, demonstrating the specificity of this PDT treatment on cancer cells. Our findings imply that the incorporation of two different cytotoxic metals in the same molecule represents a remarkable cytotoxic effect in comparison to traditional homometallic Pt(II) drugs.
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http://dx.doi.org/10.1021/acs.inorgchem.9b01981DOI Listing
September 2019

Can Heterocyclic γ-Peptides Provide Polyfunctional Platforms for Synthetic Glycocluster Construction?

Chemistry 2018 Aug 9;24(44):11426-11432. Epub 2018 Jul 9.

Institut des Biomolécules Max Mousseron, UMR CNRS-UM-ENSCM 5247, UFR des Sciences Pharmaceutiques et Biologiques, 15 Avenue Charles Flahault, 34093, Montpellier Cedex 5, France.

Sugars play key roles in many molecular and cellular communication processes involving a family of proteins named lectins. The low affinity associated with sugar recognition is generally counterbalanced by the multivalent nature of the interaction. While many polyglycosylated architectures have been described, only a few studies focused on the impact of topology variations of the multivalent structures on the interaction with lectin proteins. One major interest of our group concerns the design of new highly predictable and stable molecular pseudo-peptide architectures for therapeutic applications. In such a context, we described a class of constrained heterocyclic γ-amino acids built around a thiazole ring, named ATCs. ATC oligomers are helical molecules resulting from the formation of a highly stable C hydrogen-bonding pattern. Following our program, we herein address the potential of ATC oligomers as tunable scaffolds for the development of original multivalent glycoclusters.
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http://dx.doi.org/10.1002/chem.201802032DOI Listing
August 2018

Multifunctional manganese-doped Prussian blue nanoparticles for two-photon photothermal therapy and magnetic resonance imaging.

Photodiagnosis Photodyn Ther 2018 Jun 22;22:65-69. Epub 2018 Feb 22.

Institut des Biomolécules Max Mousseron, UMR5247, Université de Montpellier, CNRS, ENSCM, Faculté de Pharmacie, 15 Avenue Charles Flahault, 34093, Montpellier, Cedex 05, France. Electronic address:

Here we demonstrate for the first time that Mn-doped Prussian blue nanoparticles of c.a. 70 nm act as effective agents for photothermal therapy under two-photon excitation with an almost total eradication of malignant cells (97 and 98%) at a concentration of 100 μg mL 24 h after NIR excitation. This effect combined with interesting longitudinal NMR relaxivity values offer new perspectives for effective imaging and cancer treatment.
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http://dx.doi.org/10.1016/j.pdpdt.2018.02.015DOI Listing
June 2018

Cell compatibility of a maghemite/polymer biomedical nanoplatform.

Toxicol In Vitro 2015 Aug 16;29(5):962-75. Epub 2015 Apr 16.

Department of Toxicology, University of Zaragoza, Veterinary Faculty, C/Miguel Servet 177, E50013 Zaragoza, Spain. Electronic address:

We are reporting the cytocompatibility and cellular fate of an iron oxide/polymer nanoplatform (IONP) in its most basic formulation, using both mesenchymal (vascular smooth muscle cells, VSMC), and epithelial (opossum kidney, OK) cells. The cytotoxicity and cell internalization of the nanoplatform has been evaluated in relation to time of exposure and concentration of different components. A series of samples with different iron oxide nanoparticle, sizes, hydrodynamic sizes and iron/polymer ratio have been examined. In all cases cytotoxicity is low, and it is mostly determined by the internalization rate, being higher in VSMC than in OK cells. The mean lethal dose has a very narrow threshold, and necrosis is the only cell death type. IONP uptake shows little incidence on oxidative stress, and inflammasome activation is only observed with the smaller IONP at high concentration. The internalization rate in VSMC is determined by the polymer concentration exclusively. In OK cells, internalization rate seems to increase with decreasing hydrodynamic size. Internalization occurs through clathrin-dependent endocytosis, as it is prevented by potassium depletion and chlorpromazine. IONP are directed and accumulated in lysosomes. Under IONP overload, lysosomal dysfunction would cause cell death using concentrations that are hardly achieved in vivo.
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http://dx.doi.org/10.1016/j.tiv.2015.04.003DOI Listing
August 2015

Hemostasis disorders caused by polymer coated iron oxide nanoparticles.

J Biomed Nanotechnol 2013 Jul;9(7):1272-85

instituto de Ciencia de Materiales de Aragón, CSIC - Universidad de Zaragoza, and Departamento de Física de la Materia Condensada, Facultad de Ciencias, 50009 Zaragoza, Spain.

Background: Superparamagnetic iron oxide nanoparticles (SPIONs) are inorganic nanomaterials gaining strong clinical interest due to their increasing number of biological and medical applications. The stabilization of SPIONs in a biocompatible stable suspension (bioferrofluid) is generally achieved by an adequate polymeric coating. As many applications using these materials are intended for clinical use through intravenous injection, it is of outmost importance to evaluate their hemostatic behaviour.

Objectives: The aim of this work is to evaluate the hemocompatibility of selected polymer coated bioferrofluids and of their separated components by observing the effects of the bioferrofluid on: the coagulation process--by measuring the prothrombin time (PT) and activated partial thromboplastin time (aPTT)--, the complete blood count (CBC)--Erythrocytes, Leucocytes, Platelets, Hemoglobin and hematocrit--and the hemolysis.

Methods: A SPIONs/bioferrofluid model consisting of a magnetic core of iron oxide nanoparticles embedded within poly(4-vinyl pyridine) (P4VP) and all coated with polyethylene glycol (PEG) has been selected.

Results And Conclusions: By increasing the concentration of the bioferrofluids an inhibitory effect on the intrinsic pathway of blood coagulation is observed, as indicated by significant increase in aPTT in vitro while PT values stay normal. The effect of the coating components on the inhibition of blood coagulation process shows that PEG has no effect on the process while the P4VP-g-PEG copolymer coating has a strong anticoagulant effect indicating that P4VP is at the origin of such effects. The studied bioferrofluids have no effect on the CBC neither they show in vitro hemolytic effect on blood.
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http://dx.doi.org/10.1166/jbn.2013.1637DOI Listing
July 2013
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