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1.
Nanoscale ; 16(33): 15585-15614, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39104307

RESUMEN

Core-shell nanocomposites made of iron oxide core (IO NPs) coated with mesoporous silica (MS) shells are promising theranostic agents. While the core is being used as an efficient heating nanoagent under alternating magnetic field (AMF) and near infra-red (NIR) light and as a suitable contrast agent for magnetic resonance imaging (MRI), the MS shell is particularly relevant to ensure colloidal stability in a biological buffer and to transport a variety of therapeutics. However, a major challenge with such inorganic nanostructures is the design of adjustable silica structures, especially with tunable large pores which would be useful, for instance, for the delivery of large therapeutic biomolecule loading and further sustained release. Furthermore, the effect of tailoring a porous silica structure on the magneto- or photothermal dissipation still remains poorly investigated. In this work, we undertake an in-depth investigation of the growth of stellate mesoporous silica (STMS) shells around IO NPs cores and of their micro/mesoporous features respectively through time-lapse and in situ liquid phase transmission electron microscopy (LPTEM) and detailed nitrogen isotherm adsorption studies. We found here that the STMS shell features (thickness, pore size, surface area) can be finely tuned by simply controlling the sol-gel reaction time, affording a novel range of IO@STMS core@shell NPs. Finally, regarding the responses under alternating magnetic fields and NIR light which are evaluated as a function of the silica structure, IO@STMS NPs having a tunable silica shell structure are shown to be efficient as T2-weighted MRI agents and as heating agents for magneto- and photoinduced hyperthermia. Furthermore, such IO@STMS are found to display anti-cancer effects in pancreatic cancer cells under magnetic fields (both alternating and rotating).


Asunto(s)
Compuestos Férricos , Hipertermia Inducida , Imagen por Resonancia Magnética , Nanocompuestos , Dióxido de Silicio , Dióxido de Silicio/química , Nanocompuestos/química , Porosidad , Humanos , Compuestos Férricos/química , Línea Celular Tumoral , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Medios de Contraste/química , Medios de Contraste/farmacología
2.
Chemphyschem ; : e202400023, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39046870

RESUMEN

Iron oxide nanoflowers (IONFs) that display singular magnetic properties can be synthesized through a polyol route first introduced almost 2 decades ago by Caruntu et al, presenting a multi-core morphology in which several grains (around 10 nm) are attached together and sintered. These outstanding properties are of great interest for magnetic field hyperthermia, which is considered as a promising therapy against cancer. Although of significantly smaller diameter, the specific adsorption rate (SAR) of IONFs reach values as large as for "magnetosomes" that are natural magnetic nanoparticles typically ~40 nm found in certain bacteria, which can be grown artificially but with much lower yield compared to chemical synthesis such as the polyol route. This work aims at better understanding the structure-property relationships, linking the internal IONF nanostructure as observed by HR-TEM to their magnetic properties. A library of mono- and multicore IONFs is presented, with diameters ranging from 11 to 30 nm in a narrow size distribution. More particularly, by relating their structural features to their magnetic properties investigated by utilizing AC magnetometry over a wide range of alternating magnetic field conditions, we showed that the SAR values of all synthesized batches vary with overall diameter and number of constituting cores.

3.
J Mater Chem B ; 8(46): 10527-10539, 2020 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-33179706

RESUMEN

Nanoparticle induced hyperthermia has been considered as a promising approach for cancer treatment for decades. The local heating ability and drug delivery potential highlight a diversified possibility in clinical application, therefore a variety of nanoparticles has been developed accordingly. However, currently, only a few of them are translated into the clinical stage indicating a 'medically underexplored nanoparticles' situation, which encourages their comprehensive biomedical exploration. This study presents a thorough biological evaluation of previous well-developed dual pH- and thermo-responsive magnetic doxorubicin-nanocarriers (MNC-DOX) in multiple cancer cell lines. The cytotoxicity of the nanocomposites has been determined by the MTT assay on primary cell lines. Histology and fluorescence microscopy imaging revealed the efficiency of cellular uptake of nanocarriers in different cell lines. The IC50 of MNC-DOX is significantly higher than that of free DOX without an alternating magnetic field (AMF), which implied the potential to lower the systemic cytotoxicity in clinical research. The concurrent thermo-chemotherapy generated by this platform has been successfully achieved under an AMF. Promising effective synergistic results have been demonstrated through in vitro study in multi-model cancer cell lines via both trypan blue exclusion and bioluminescence imaging methods. Furthermore, the two most used magnetic hyperthermia modalities, namely intracellular and extracellular treatments, have been compared on the same nanocarriers in all 3 cell lines, which showed that treatment after internalization is not required but preferable. These results lead to the conclusion that this dual responsive nanocarrier has extraordinary potential to serve as a novel broad-spectrum anticancer drug and worth pursuing for potential clinical applications.


Asunto(s)
Antineoplásicos/farmacología , Doxorrubicina/farmacología , Portadores de Fármacos/química , Nanopartículas de Magnetita/química , Nanocompuestos/química , Animales , Línea Celular Tumoral , Portadores de Fármacos/toxicidad , Ensayos de Selección de Medicamentos Antitumorales , Fibroblastos/efectos de los fármacos , Humanos , Concentración de Iones de Hidrógeno , Hipertermia Inducida/métodos , Campos Magnéticos , Nanopartículas de Magnetita/toxicidad , Ratones , Nanocompuestos/toxicidad , Temperatura
4.
Mater Sci Eng C Mater Biol Appl ; 104: 109920, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31500039

RESUMEN

HYPOTHESIS: Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as building block of colloidal nanocomposites for biomedical applications. Strategies employed to embed them in a biodegradable and biocompatible polymer matrix often fail to achieve a high density of loading which would greatly benefit to applications such as imaging and hyperthermia. In this study, poly(acrylic acid) coated SPION (γ-Fe2O3-PAA) are self-assembled with hydrolysable poly(serine ester) by electrostatic complexation, leading to perfectly defined spherical particles with ultra-high density of magnetic material and an ability to auto-degrade into individual SPION and biocompatible byproducts. EXPERIMENTS: Self-assembly and auto-degradation of γ-Fe2O3-PAA/poly(serine ester) and γ-Fe2O3-PAA/poly(serine ester)-b-PEG colloidal particles are studied by light scattering and microscopy. Colloidal stability in bio-fluids, hyperthermia under alternating magnetic field, cellular uptake, cytotoxicity and degradation of γ-Fe2O3-PAA/poly(serine ester)-b-PEG in living cells are investigated. FINDINGS: A remarkably slow electrostatic complexation leads to dense superparamagnetic γ-Fe2O3-PAA/poly(serine ester)-b-PEG polyion complexes (PICs) with controlled sizes (150-500 nm) and times of degradation in aqueous solvents (700-5000 h). The material shows good sustainability during hyperthermia, is well taken up by MC3T3 cells and non-cytotoxic. TEM images reveal a mechanism of degradation by "peeling" and fragmentation. In cells, PICs are reduced into individual SPIONs within 72 h.


Asunto(s)
Materiales Biocompatibles/química , Coloides/química , Fenómenos Magnéticos , Nanopartículas de Magnetita/química , Péptidos/química , Polímeros/química , Resinas Acrílicas/síntesis química , Resinas Acrílicas/química , Animales , Dispersión Dinámica de Luz , Células Hep G2 , Humanos , Hipertermia Inducida , Ratones , Péptidos/síntesis química , Polietilenglicoles/síntesis química , Polietilenglicoles/química , Polímeros/síntesis química , Pruebas de Toxicidad
5.
J Mater Chem B ; 7(30): 4692-4705, 2019 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-31364686

RESUMEN

The present study reports the preparation of poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-b-PCL) polymer vesicles via a nanoprecipitation method and the loading of two different size hydrophobically coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (a magnetic core size of 4.2 nm and 7.6 nm) into the membrane of these nanovesicles, whose thickness was measured precisely by small angle neutron scattering (SANS). Spherical nano-assemblies with a high USPIO payload and a diameter close to 150 nm were obtained as confirmed by dynamic light scattering (DLS), transmission electron microscopy (TEM) and cryo-TEM. The vesicular structure of these hybrid nano-assemblies was confirmed by multi-angle light scattering (MALS) measurements. Their magnetic properties were evaluated by T1 and T2 measurements (20 and 60 MHz) and by nuclear magnetic relaxation dispersion (NMRD) profiles. The size of USPIO entrapped in the membranes of PEO-b-PCL vesicles has a strong impact on their magnetic properties. It affects both their longitudinal and their transverse relaxivities and thus their magnetic resonance imaging (MRI) sensitivity. Acid-catalyzed hydrolysis of the PCL membrane also influences their relaxivities as shown by measurements carried out at pH 7 vs. pH 5. This property was used to monitor the membrane hydrolytic degradation in vitro, as a proof of concept of potential monitoring of drug delivery by nanomedicines in vivo and non-invasively, by MRI.


Asunto(s)
Sistemas de Liberación de Medicamentos , Imagen por Resonancia Magnética/métodos , Nanopartículas de Magnetita/química , Membranas Artificiales , Monitoreo de Drogas/métodos , Compuestos Férricos , Concentración de Iones de Hidrógeno , Hidrólisis , Poliésteres , Prueba de Estudio Conceptual
6.
Nanomaterials (Basel) ; 8(12)2018 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-30563227

RESUMEN

Magnetic nanoparticles (MNPs) of magnetite (Fe3O4) were prepared using a polystyrene-graft-poly(2-vinylpyridine) copolymer (denoted G0PS-g-P2VP or G1) as template. These MNPs were subjected to self-assembly with a poly(acrylic acid)-block-poly(2-hydroxyethyl acrylate) double-hydrophilic block copolymer (DHBC), PAA-b-PHEA, to form water-dispersible magnetic polyion complex (MPIC) micelles. Large Fe3O4 crystallites were visualized by transmission electron microscopy (TEM) and magnetic suspensions of MPIC micelles exhibited improved colloidal stability in aqueous environments over a wide pH and ionic strength range. Biological cells incubated for 48 h with MPIC micelles at the highest concentration (1250 µg of Fe3O4 per mL) had a cell viability of 91%, as compared with 51% when incubated with bare (unprotected) MNPs. Cell internalization, visualized by confocal laser scanning microscopy (CLSM) and TEM, exhibited strong dependence on the MPIC micelle concentration and incubation time, as also evidenced by fluorescence-activated cell sorting (FACS). The usefulness of MPIC micelles for cellular radiofrequency magnetic field hyperthermia (MFH) was also confirmed, as the MPIC micelles showed a dual dose-dependent effect (concentration and duration of magnetic field exposure) on the viability of L929 mouse fibroblasts and U87 human glioblastoma epithelial cells.

7.
Nanomaterials (Basel) ; 8(8)2018 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-30126110

RESUMEN

In this work, we have studied field-induced aggregation and magnetic separation-realized in a microfluidic channel equipped with a single magnetizable micropillar-of multicore iron oxide nanoparticles (IONPs) also called "nanoflowers" of an average size of 27 ± 4 nm and covered by either a citrate or polyethylene (PEG) monolayer having a thickness of 0.2⁻1 nm and 3.4⁻7.8 nm, respectively. The thickness of the adsorbed molecular layer is shown to strongly affect the magnetic dipolar coupling parameter because thicker molecular layers result in larger separation distances between nanoparticle metal oxide multicores thus decreasing dipolar magnetic forces between them. This simple geometrical constraint effect leads to the following important features related to the aggregation and magnetic separation processes: (a) Thinner citrate layer on the IONP surface promotes faster and stronger field-induced aggregation resulting in longer and thicker bulk needle-like aggregates as compared to those obtained with a thicker PEG layer; (b) A stronger aggregation of citrated IONPs leads to an enhanced retention capacity of these IONPs by a magnetized micropillar during magnetic separation. However, the capture efficiency Λ at the beginning of the magnetic separation seems to be almost independent of the adsorbed layer thickness. This is explained by the fact that only a small portion of nanoparticles composes bulk aggregates, while the main part of nanoparticles forms chains whose capture efficiency is independent of the adsorbed layer thickness but depends solely on the Mason number Ma. More precisely, the capture efficiency shows a power law trend Λ âˆ M a−n, with n ≈ 1.4⁻1.7 at 300 < Ma < 104, in agreement with a new theoretical model. Besides these fundamental issues, the current work shows that the multicore IONPs with a size of about 30 nm have a good potential for use in biomedical sensor applications where an efficient low-field magnetic separation is required. In these applications, the nanoparticle surface design should be carried out in a close feedback with the magnetic separation study in order to find a compromise between biological functionalities of the adsorbed molecular layer and magnetic separation efficiency.

8.
Inorg Chem ; 56(14): 8232-8243, 2017 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-28671822

RESUMEN

The polyol route is a versatile and up-scalable method to produce large batches of iron oxide nanoparticles with well-defined structures and magnetic properties. Importance of parameters such as temperature and reaction time, heating profile, nature of the polyol solvent or organometallic precursors on nanostructure and properties has already been described in the literature. Yet, the crucial role of water in the forced hydrolysis pathway has never been reported, despite its mandatory presence for nanoparticle production. This communication investigates the influence of the water amount and temperature at which it is injected in the reflux system for either a pure polyol solvent system or a mixture with poly(hydroxy)amine. Distinct morphologies of nanoparticles were thereby obtained, from ultra-ultra-small smooth spheres down to 4 nm in diameter to larger ones up to 37 nm. Well-defined multicore assemblies with narrow grain size dispersity termed nanoflowers were also synthesized. A diverse and large library of samples was obtained by manipulating the nature of solvents and the amount of added water while keeping all other parameters constant. The different morphologies lead to magnetic nanoparticles suitable for important biomedical applications such as magnetic hyperthermia, magnetic resonance imaging (MRI) contrast agent, or both.

9.
Sci Rep ; 7(1): 4794, 2017 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-28684775

RESUMEN

We present a versatile continuous microfluidic flow-focusing method for the production of Doxorubicin (DOX) or Tamoxifen (TAM)-loaded poly(D,L-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs). We use a partially water-miscible solvent mixture (dimethyl sulfoxide DMSO+ dichloromethane DCM) as precursor drug/polymer solution for NPs nucleation. We extrude this partially water-miscible solution into an aqueous medium and synthesized uniform PLGA NPs with higher drug loading ability and longer sustained-release ability than conventional microfluidic or batch preparation methods. The size of NPs could be precisely tuned by changing the flow rate ratios, polymer concentration, and volume ratio of DCM to DMSO (VDCM/VDMSO) in the precursor emulsion. We investigated the mechanism of the formation of NPs and the effect of VDCM/VDMSO on drug release kinetics. Our work suggests that this original, rapid, facile, efficient and low-cost method is a promising technology for high throughput NP fabrication. For the two tested drugs, one hydrophilic (Doxorubicin) the other one hydrophobic (Tamoxifen), encapsulation efficiency (EE) as high as 88% and mass loading content (LC) higher than 25% were achieved. This new process could be extended as an efficient and large scale NP production method to benefit to fields like controlled drug release and nanomedicine.


Asunto(s)
Antibióticos Antineoplásicos/química , Preparaciones de Acción Retardada/química , Microfluídica/métodos , Nanopartículas/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Dimetilsulfóxido/química , Doxorrubicina/química , Composición de Medicamentos/métodos , Liberación de Fármacos , Emulsiones , Humanos , Cinética , Cloruro de Metileno/química , Nanopartículas/ultraestructura , Tamaño de la Partícula , Solventes/química , Tamoxifeno/química , Agua/química
10.
Genes (Basel) ; 8(2)2017 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-28208731

RESUMEN

The present work aims to demonstrate that colloidal dispersions of magnetic iron oxide nanoparticles stabilized with dextran macromolecules placed in an alternating magnetic field can not only produce heat, but also that these particles could be used in vivo for local and noninvasive deposition of a thermal dose sufficient to trigger thermo-induced gene expression. Iron oxide nanoparticles were first characterized in vitro on a bio-inspired setup, and then they were assayed in vivo using a transgenic mouse strain expressing the luciferase reporter gene under transcriptional control of a thermosensitive promoter. Iron oxide nanoparticles dispersions were applied topically on the mouse skin or injected subcutaneously with Matrigel™ to generate so-called pseudotumors. Temperature was monitored continuously with a feedback loop to control the power of the magnetic field generator and to avoid overheating. Thermo-induced luciferase expression was followed by bioluminescence imaging 6 h after heating. We showed that dextran-coated magnetic iron oxide nanoparticle dispersions were able to induce in vivo mild hyperthermia compatible with thermo-induced gene expression in surrounding tissues and without impairing cell viability. These data open new therapeutic perspectives for using mild magnetic hyperthermia as noninvasive modulation of tumor microenvironment by local thermo-induced gene expression or drug release.

11.
Biochim Biophys Acta Gen Subj ; 1861(6): 1617-1641, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28238734

RESUMEN

The use of an alternating magnetic field (AMF) to generate non-invasively and spatially a localized heating from a magnetic nano-mediator has become very popular these last years to develop magnetic hyperthermia (MH) as a promising therapeutic modality already used in the clinics. AMF has become highly attractive this last decade over others radiations, as AMF allows a deeper penetration in the body and a less harmful ionizing effect. In addition to pure MH which induces tumor cell death through local T elevation, this AMF-generated magneto-thermal effect can also be exploited as a relevant external stimulus to trigger a drug release from drug-loaded magnetic nanocarriers, temporally and spatially. This review article is focused especially on this concept of AMF induced drug release, possibly combined with MH. The design of such magnetically responsive drug delivery nanoplatforms requires two key and complementary components: a magnetic mediator which collects and turns the magnetic energy into local heat, and a thermoresponsive carrier ensuring thermo-induced drug release, as a consequence of magnetic stimulus. A wide panel of magnetic nanomaterials/chemistries and processes are currently developed to achieve such nanoplatforms. This review article presents a broad overview about the fundamental concepts of drug releasing nanoplatforms activated by AMF, their formulations, and their efficiency in vitro and in vivo. This article is part of a Special Issue entitled "Recent Advances in Bionanomaterials" Guest Editors: Dr. Marie-Louise Saboungi and Dr. Samuel D. Bader.


Asunto(s)
Antineoplásicos/química , Portadores de Fármacos/química , Campos Magnéticos , Magnetismo/métodos , Nanomedicina/métodos , Nanopartículas/química , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/metabolismo , Composición de Medicamentos , Liberación de Fármacos , Transferencia de Energía , Humanos , Hipertermia Inducida/métodos , Cinética , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Solubilidad
12.
Nanotechnology ; 26(1): 015704, 2015 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-25490677

RESUMEN

Magnetic nanoparticles (NPs) are intensively studied for their potential use for magnetic hyperthermia, a treatment that has passed a phase II clinical trial against severe brain cancer (glioblastoma) at the end of 2011. Their heating power, characterized by the 'specific absorption rate (SAR)', is often considered temperature independent in the literature, mainly because of the difficulties that arise from the measurement methodology. Using a dynamic magnetometer presented in a recent paper, we measure here the thermal dependence of SAR for superparamagnetic iron oxide (maghemite) NPs of four different size-ranges corresponding to mean diameters around 12 nm, 14 nm, 15 nm and 16 nm. The article reports a parametrical study extending from 10 to 60 °C in temperature, from 75 to 1031 kHz in frequency, and from 2 to 24 kA m(-1) in magnetic field strength. It was observed that SAR values of smaller NPs decrease with temperature whereas for the larger sample (16 nm) SAR values increase with temperature. The measured variation of SAR with temperature is frequency dependent. This behaviour is fully explained within the scope of linear response theory based on Néel and Brown relaxation processes, using independent magnetic measurements of the specific magnetization and the magnetic anisotropy constant. A good quantitative agreement between experimental values and theoretical values is confirmed in a tri-dimensional space that uses as coordinates the field strength, the frequency and the temperature.

13.
Adv Healthc Mater ; 2(11): 1420-4, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23606565

RESUMEN

Multifunctional polymersomes loaded with maghemite nanoparticles and grafted with an antibody, directed against human endothelial receptor 2, are developed as novel MRI contrast agents for bone metastasis imaging. Upon administration in mice bearing bone tumor grown from human breast cancer cells, MR images show targeting and enhanced retention of antibody-labeled polymersomes at the tumor site.


Asunto(s)
Anticuerpos/metabolismo , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/secundario , Fenómenos Magnéticos , Imagen por Resonancia Magnética/métodos , Polímeros/química , Animales , Línea Celular Tumoral , Compuestos Férricos/química , Humanos , Ratones , Nanopartículas/química , Distribución Tisular
14.
J Control Release ; 169(3): 165-70, 2013 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-23353805

RESUMEN

Local and temporal control of drug release has for long been a main focus in the development of novel drug carriers. Polymersomes, which can load both hydrophilic and hydrophobic species and, at the same time, be tailored to respond to a desired stimulus, have drawn much attention over the last decade. Here we describe polymersomes able to encapsulate up to 6% (w/w) of doxorubicin (DOX) together with 30% (w/w) of superparamagnetic iron oxide nanoparticles (USPIO; γ-Fe2O3). Upon internalization in HeLa cells and when a high frequency AC magnetic field (14mT at 750kHz) was applied, the developed delivery system elicited an 18% increase in cell toxicity, associated with augmented DOX release kinetics. In order to ensure that the observed cytotoxicity arose from the increased doxorubicin release and not from a pure magnetic hyperthermia effect, polymersomes loaded with magnetic nanoparticles alone were also tested. In this case, no increased toxicity was observed. We hypothesize that the magnetic field is inducing a very local hyperthermia effect at the level of the polymersome membrane, increasing drug release. This approach opens new perspectives in the development of smart delivery systems able to release drug upon demand and therefore, improving treatment control.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/química , Doxorrubicina/administración & dosificación , Nanopartículas de Magnetita/química , Neoplasias/tratamiento farmacológico , Antibióticos Antineoplásicos/farmacocinética , Antibióticos Antineoplásicos/farmacología , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Células HeLa , Humanos , Hipertermia Inducida , Campos Magnéticos , Neoplasias/terapia
15.
Faraday Discuss ; 166: 83-100, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24611270

RESUMEN

The aim of this contribution is to design, produce and characterize size-tuneable core-shell micelles from amphiphilic Tat-b-poly(trimethylene carbonate) (Tat-b-PTMC) molecular chimeras, and to explore their biological properties. Because the extensive characterization of nanomaterials is a pre-requisite to understand and rationalize their ensuing properties, we present a detailed description of Tat-b-PTMC micelles thanks to light scattering, AFM imaging and small angle neutron scattering analyses. In vitro, Tat-b-PTMC micelles were found to be rapidly and efficiently internalized by HeLa cells, with cellular uptake kinetics being mostly related to Tat peptide content and, to a lesser extent, to nanoparticle size. We also demonstrated that, after a first membrane-binding step, Tat-b-PTMC micelles were taken up by cells via an energy-dependent endocytotic process.


Asunto(s)
Biopolímeros/química , Micelas , Péptidos/química , Relación Estructura-Actividad
16.
J Mater Chem B ; 1(39): 5317-5328, 2013 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-32263334

RESUMEN

Magnetic resonance imaging (MRI) is at the forefront of non-invasive medical imaging techniques. It provides good spatial and temporal resolution that can be further improved by the use of contrast agents (CAs), providing a valuable tool for diagnostic purposes. Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are attractive MRI contrast agents due to their negative (T2) contrast enhancement capability and biocompatibility. Clusters of USPIOs with polymer material are of particular interest since they can sustain additional functionalities like drug delivery and targeting. Aiming to establish a relationship between the morphology of the clusters and their efficacy as MRI contrast agents (relaxometric properties), we prepared - using three different maghemite (γ-Fe2O3) USPIO diameters - a series of hybrid copolymer/iron oxide CAs presenting two different geometries (micellar or vesicular). The NMR relaxometry profiles confirmed the nature of the physical mechanisms inducing the increase of nuclear relaxation rates at low (magnetic anisotropy) and high (Curie relaxation) magnetic fields. A heuristic model, first proposed by Roch, Muller, Gillis, and Brooks, allowed the fitting of the whole longitudinal relaxivity r1(ν) profile, for samples with different magnetic core sizes. We show that both types of clusters exhibit transverse relaxivity (r2) values comparable to or higher than those of common contrast agents, over the whole tested frequency range. Moreover, in-depth analysis revealed substantially a linear relationship between r2 and the number of encapsulated USPIOs divided by the diameter of the clusters (NUSPIO/DH), for each USPIO size. The cluster structure (i.e. micelle or vesicle) appeared to have a mild influence on the transverse relaxivity value. Indeed, the r2 value was mainly governed by the individual size of the USPIOs, correlated with both the cluster external diameter and the magnetic material volume fraction.

17.
ACS Nano ; 5(2): 1122-40, 2011 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-21218795

RESUMEN

Hydrophobically modified maghemite (γ-Fe(2)O(3)) nanoparticles were encapsulated within the membrane of poly(trimethylene carbonate)-b-poly(l-glutamic acid) (PTMC-b-PGA) block copolymer vesicles using a nanoprecipitation process. This formation method gives simple access to highly magnetic nanoparticles (MNPs) (loaded up to 70 wt %) together with good control over the vesicles size (100-400 nm). The simultaneous loading of maghemite nanoparticles and doxorubicin was also achieved by nanoprecipitation. The deformation of the vesicle membrane under an applied magnetic field has been evidenced by small angle neutron scattering. These superparamagnetic hybrid self-assemblies display enhanced contrast properties that open potential applications for magnetic resonance imaging. They can also be guided in a magnetic field gradient. The feasibility of controlled drug release by radio frequency magnetic hyperthermia was demonstrated in the case of encapsulated doxorubicin molecules, showing the viability of the concept of magneto-chemotherapy. These magnetic polymersomes can be used as efficient multifunctional nanocarriers for combined therapy and imaging.


Asunto(s)
Antineoplásicos/química , Doxorrubicina/química , Magnetoterapia/métodos , Imagen por Resonancia Magnética/métodos , Magnetismo , Nanoestructuras , Polímeros , Antineoplásicos/metabolismo , Antineoplásicos/uso terapéutico , Materiales Biocompatibles/química , Precipitación Química , Medios de Contraste , Dioxanos/química , Doxorrubicina/metabolismo , Doxorrubicina/uso terapéutico , Portadores de Fármacos/química , Compuestos Férricos/química , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Hipertermia Inducida , Membranas Artificiales , Movimiento (Física) , Nanoestructuras/química , Ácido Poliglutámico/química , Polímeros/química
18.
Chem Commun (Camb) ; (15): 1783-5, 2008 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-18379692

RESUMEN

A millimetric coaxial flow device operating under laminar flow has been designed to study the synthesis of iron oxide nanoparticles in a millichannel where the flow rate of the different reagents has been adjusted all over the experiments so that the magnetic and stable colloidal iron oxide particles with a size less than 7 nm have been prepared continuously.

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