RESUMO
While magnetic nanoparticles offer exciting possibilities for stem cell imaging or tissue bioengineering, their long-term intracellular fate remains to be fully documented. Besides, it appears that magnetic nanoparticles can occur naturally in human cells, but their origin and potentially endogenous synthesis still need further understanding. In an effort to explore the life cycle of magnetic nanoparticles, we investigated their transformations upon internalization in mesenchymal stem cells and as a function of the cells' differentiation status (undifferentiated, or undergoing adipogenesis, osteogenesis, and chondrogenesis). Using magnetism as a fingerprint of the transformation process, we evidenced an important degradation of the nanoparticles during chondrogenesis. For the other pathways, stem cells were remarkably "remagnetized" after degradation of nanoparticles. This remagnetization phenomenon is the direct demonstration of a possible neosynthesis of magnetic nanoparticles in cellulo and could lay some foundation to understand the presence of magnetic crystals in human cells. The neosynthesis was shown to take place within the endosomes and to involve the H-subunit of ferritin. Moreover, it appeared to be the key process to avoid long-term cytotoxicity (impact on differentiation) related to high doses of magnetic nanoparticles within stem cells.
Assuntos
Diferenciação Celular , Condrogênese , Endossomos/metabolismo , Campos Magnéticos , Nanopartículas de Magnetita , Células-Tronco Mesenquimais/metabolismo , Humanos , Células-Tronco Mesenquimais/citologiaRESUMO
Nanoparticle-mediated thermal treatments have demonstrated high efficacy and versatility as a local anticancer strategy beyond traditional global hyperthermia. Nanoparticles act as heating generators that can trigger therapeutic responses at both the cell and tissue level. In some cases, treatment happens in the absence of a global temperature rise, damaging the tumor cells even more selectively than other nanotherapeutic strategies. The precise determination of the local temperature in the vicinity of such nanoheaters then stands at the heart of thermal approaches to better adjust the therapeutic thermal onset and reduce potential toxicity-related aspects. Herein, we describe an experimental procedure by X-ray absorption spectroscopy, which directly and accurately infers the local temperature of gold-based nanoparticles, single and hybrid nanocrystals, upon laser photoexcitation, revealing significant nanothermal gradients. Such nanothermometric methodology based on the temperature-dependency of atomic parameters of nanoparticles can be extended to any nanosystem upon remote hyperthermal conditions.
Assuntos
Hipertermia Induzida , Nanopartículas , Ouro , Lasers , Temperatura , Espectroscopia por Absorção de Raios XRESUMO
Considerable knowledge has been acquired in inorganic nanoparticles' synthesis and nanoparticles' potential use in biomedical applications. Among different materials, iron oxide nanoparticles remain unrivaled for several reasons. Not only do they respond to multiple physical stimuli (e.g., magnetism, light) and exert multifunctional therapeutic and diagnostic actions but also they are biocompatible and integrate endogenous iron-related metabolic pathways. With the aim to optimize the use of (magnetic) iron oxide nanoparticles in biomedicine, different biophysical phenomena have been recently identified and studied. Among them, the concept of a "nanoparticle's identity" is of particular importance. Nanoparticles' identities evolve in distinct biological environments and over different periods of time. In this Account, we focus on the remodeling of magnetic nanoparticles' identities following their journey inside cells. For instance, nanoparticles' functions, such as heat generation or magnetic resonance imaging, can be highly impacted by endosomal confinement. Structural degradation of nanoparticles was also evidenced and quantified in cellulo and correlates with the loss of magnetic nanoparticle properties. Remarkably, in human stem cells, the nonmagnetic products of nanoparticles' degradation could be subsequently reassembled into neosynthesized, endogenous magnetic nanoparticles. This stunning occurrence might account for the natural presence of magnetic particles in human organs, especially the brain. However, mechanistic details and the implication of such phenomena in homeostasis and disease have yet to be completely unraveled.This Account aims to assess the short- and long-term transformations of magnetic iron oxide nanoparticles in living cells, particularly focusing on human stem cells. Precisely, we herein overview the multiple and ever-evolving chemical, physical, and biological magnetic nanoparticles' identities and emphasize the remarkable intracellular fate of these nanoparticles.
Assuntos
Endossomos/metabolismo , Nanopartículas Magnéticas de Óxido de Ferro/química , Encéfalo/diagnóstico por imagem , Cristalização , Eletroencefalografia , Humanos , Hipertermia Induzida , Ferro/metabolismo , Imageamento por Ressonância Magnética , Nanomedicina , Células-Tronco/química , Células-Tronco/citologia , Células-Tronco/metabolismo , Engenharia TecidualRESUMO
BACKGROUND: The interactions between nanoparticles and the biological environment have long been studied, with toxicological assays being the most common experimental route. In parallel, recent growing evidence has brought into light the important role that cell mechanics play in numerous cell biological processes. However, despite the prevalence of nanotechnology applications in biology, and in particular the increased use of magnetic nanoparticles for cell therapy and imaging, the impact of nanoparticles on the cells' mechanical properties remains poorly understood. RESULTS: Here, we used a parallel plate rheometer to measure the impact of magnetic nanoparticles on the viscoelastic modulus G*(f) of individual cells. We show how the active uptake of nanoparticles translates into cell stiffening in a short time scale (< 30 min), at the single cell level. The cell stiffening effect is however less marked at the cell population level, when the cells are pre-labeled under a longer incubation time (2 h) with nanoparticles. 24 h later, the stiffening effect is no more present. Imaging of the nanoparticle uptake reveals almost immediate (within minutes) nanoparticle aggregation at the cell membrane, triggering early endocytosis, whereas nanoparticles are almost all confined in late or lysosomal endosomes after 2 h of uptake. Remarkably, this correlates well with the imaging of the actin cytoskeleton, with actin bundling being highly prevalent at early time points into the exposure to the nanoparticles, an effect that renormalizes after longer periods. CONCLUSIONS: Overall, this work evidences that magnetic nanoparticle internalization, coupled to cytoskeleton remodeling, contributes to a change in the cell mechanical properties within minutes of their initial contact, leading to an increase in cell rigidity. This effect appears to be transient, reduced after hours and disappearing 24 h after the internalization has taken place.
Assuntos
Nanopartículas de Magnetita , Nanopartículas/metabolismo , Nanotecnologia/métodos , Análise de Célula Única/métodos , Membrana Celular , Citoesqueleto/metabolismo , Elasticidade , Endocitose , Endossomos/metabolismo , Humanos , Lisossomos , Microscopia Eletrônica de Transmissão , Reologia , Resistência ao Cisalhamento , Estresse MecânicoRESUMO
BACKGROUND: Despite the highly expected clinical application of nanoparticles (NPs), the translation of NPs from lab to the clinic has been relatively slow. Co-culture 3D spheroids account for the 3D arrangement of tumor cells and stromal components, e.g., cancer-associated fibroblasts (CAFs) and extracellular matrix, recapitulating microenvironment of head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated how the stroma-rich tumor microenvironment affects the uptake, penetration, and photodynamic efficiency of three lipid-based nanoformulations of approved in EU photosensitizer temoporfin (mTHPC): Foslip® (mTHPC in conventional liposomes), drug-in-cyclodextrin-in-liposomes (mTHPC-DCL) and extracellular vesicles (mTHPC-EVs). RESULTS: Collagen expression in co-culture stroma-rich 3D HNSCC spheroids correlates with the amount of CAFs (MeWo cells) in individual spheroid. The assessment of mTHPC loading demonstrated that Foslip®, mTHPC-DCL and mTHPC-EVs encapsulated 0.05 × 10- 15 g, 0.07 × 10- 15 g, and 1.3 × 10- 15 g of mTHPC per nanovesicle, respectively. The mid-penetration depth of mTHPC NPs in spheroids was 47.8 µm (Foslip®), 87.8 µm (mTHPC-DCL), and 49.7 µm (mTHPC-EVs), irrespective of the percentage of stromal components. The cellular uptake of Foslip® and mTHPC-DCL was significantly higher in stroma-rich co-culture spheroids and was increasing upon the addition of serum in the culture medium. Importantly, we observed no significant difference between PDT effect in monoculture and co-culture spheroids treated with lipid-based NPs. Overall, in all types of spheroids mTHPC-EVs demonstrated outstanding total cellular uptake and PDT efficiency comparable to other NPs. CONCLUSIONS: The stromal microenvironment strongly affects the uptake of NPs, while the penetration and PDT efficacy are less sensitive to the presence of stromal components. mTHPC-EVs outperform other lipid nanovesicles due to the extremely high loading capacity. The results of the present study enlarge our understanding of how stroma components affect the delivery of NPs into the tumors.
Assuntos
Neoplasias de Cabeça e Pescoço/metabolismo , Metabolismo dos Lipídeos , Mesoporfirinas/metabolismo , Fotoquimioterapia/métodos , Carcinoma , Técnicas de Cocultura , Matriz Extracelular , Vesículas Extracelulares , Células HT29 , Humanos , Lipídeos , Lipossomos , Nanopartículas , Fármacos Fotossensibilizantes/uso terapêutico , Esferoides Celulares , Microambiente TumoralRESUMO
Progress of thermal tumor therapies and their translation into clinical practice are limited by insufficient nanoparticle concentration to release therapeutic heating at the tumor site after systemic administration. Herein, the use of Janus magneto-plasmonic nanoparticles, made of gold nanostars and iron oxide nanospheres, as efficient therapeutic nanoheaters whose on-site delivery can be improved by magnetic targeting, is proposed. Single and combined magneto- and photo-thermal heating properties of Janus nanoparticles render them as compelling heating elements, depending on the nanoparticle dose, magnetic lobe size, and milieu conditions. In cancer cells, a much more effective effect is observed for photothermia compared to magnetic hyperthermia, while combination of the two modalities into a magneto-photothermal treatment results in a synergistic cytotoxic effect in vitro. The high potential of the Janus nanoparticles for magnetic guiding confirms them to be excellent nanostructures for in vivo magnetically enhanced photothermal therapy, leading to efficient tumor growth inhibition.
Assuntos
Hipertermia Induzida , Nanopartículas Multifuncionais , Nanopartículas , Neoplasias , Linhagem Celular Tumoral , Ouro , Campos Magnéticos , Magnetismo , Neoplasias/terapia , FototerapiaRESUMO
In order to provide insight into how anisotropic nano-objects interact with living cell membranes, and possibly self-assemble, magnetic nanorods with an average size of around 100 nm × 1 µm are designed by assembling iron oxide nanocubes within a polymeric matrix under a magnetic field. The nano-bio interface at the cell membrane under the influence of a rotating magnetic field is then explored. A complex structuration of the nanorods intertwined with the membranes is observed. Unexpectedly, after a magnetic rotating stimulation, the resulting macrorods are able to rotate freely for multiple rotations, revealing the creation of a biomagnetic torsion pendulum.
Assuntos
Membrana Celular , Nanopartículas de Magnetita/química , Nanotubos/química , Polímeros/química , Rotação , Torção Mecânica , Membrana Celular/química , Membrana Celular/efeitos dos fármacos , Humanos , Campos Magnéticos , Células PC-3 , Fenômenos Físicos , Polimerização , Polímeros/farmacologiaRESUMO
Intracellular trafficking mainly takes place along the microtubules, and its efficiency depends on the local architecture and organization of the cytoskeletal network. In this work, the cytoplasm of stem cells is subjected to mechanical vortexing at a frequency of up to 1 Hz, by using magnetic chains of endosomes embedded in the cell body, in order to locally perturb the network structure. The consequences are evaluated on the directionality and processivity of the spontaneous motion of endosomes. When the same chains are used both to shear the cell medium and to probe the intracellular traffic, a substantial decrease in transport efficiency is detected after applying the mechanical shear. Interestingly, when using different objects to apply the shear and to probe the spontaneous motion, no alteration of the transport efficiency can be detected. We conclude that shaking the vesicles mainly causes their unbinding from the cytoskeletal tracks, but has little influence on the integrity of the network itself. This is corroborated by active microrheology measurements, performed with chains actuated by a magnetic field, and showing that the mechanical compliance of the cytoplasm is similar before and after slow vortexing.
Assuntos
Espaço Intracelular/metabolismo , Resistência ao Cisalhamento , Estresse Mecânico , Transporte Biológico , Fenômenos Biomecânicos , Citoesqueleto/metabolismo , Endossomos/metabolismo , Humanos , Fenômenos Magnéticos , Células-Tronco Mesenquimais/citologia , ReologiaRESUMO
Cellular aggregates (spheroids) are widely used in biophysics and tissue engineering as model systems for biological tissues. In this Letter we propose novel methods for molding stem-cell spheroids, deforming them, and measuring their interfacial and elastic properties with a single method based on cell tagging with magnetic nanoparticles and application of a magnetic field gradient. Magnetic molding yields spheroids of unprecedented sizes (up to a few mm in diameter) and preserves tissue integrity. On subjecting these spheroids to magnetic flattening (over 150g), we observed a size-dependent elastocapillary transition with two modes of deformation: liquid-drop-like behavior for small spheroids, and elastic-sphere-like behavior for larger spheroids, followed by relaxation to a liquidlike drop.
Assuntos
Magnetismo/métodos , Células-Tronco Mesenquimais/citologia , Modelos Biológicos , Células-Tronco Pluripotentes/citologia , Esferoides Celulares/citologia , Agregação Celular , Comunicação Celular , Humanos , Microscopia Confocal/métodosRESUMO
OBJECTIVE: The purpose of this study was to detect labeled mural cells in vivo and study their therapeutic effect on tumor growth and on functional changes in the vascular network by use of MRI and fibered confocal fluorescence microscopy (FCFM). MATERIALS AND METHODS: Twenty-eight mice were allocated to the following three groups 7 days after injection of TC1 tumor cells (C157 black 6): control, no injection (n = 7); sham, injection of phosphate-buffered saline solution (n = 10); and treated, injection of human mural cells (n = 11). Tumor growth was measured with calipers. Labeled mural cells were tracked with high-resolution MRI and FCFM. Microvessel density was assessed with MRI and FCFM, and the findings were compared with the histologic results. RESULTS: Tumor growth was significantly slowed in the treated group starting on day 10 (p = 0.001). Round signal-intensity voids were observed in the center of six of seven tumors treated with magnetically labeled mural cells. Positive staining for iron was observed in histologic sections of two of five of these tumors. Microvessel density measured with FCFM was greater in the treated mice (p = 0.03). Flow cytometry revealed viable human mural cells only in treated tumors. CONCLUSION: In this study, imaging techniques such as high-resolution MRI and FCFM showed the therapeutic effect of mural cell injection on tumor growth and microvessel function.
Assuntos
Imageamento por Ressonância Magnética/métodos , Microscopia Confocal , Neovascularização Patológica/patologia , Pericitos/fisiologia , Animais , Células Cultivadas , Meios de Contraste/administração & dosagem , Modelos Animais de Doenças , Citometria de Fluxo , Humanos , Processamento de Imagem Assistida por Computador , Camundongos , Microcirculação , Células Tumorais CultivadasRESUMO
Inspired by microvesicle-mediated intercellular communication, we propose a hybrid vector for magnetic drug delivery. It consists of macrophage-derived microvesicles engineered to enclose different therapeutic agents together with iron oxide nanoparticles. Here, we investigated in vitro how magnetic nanoparticles may influence the vector effectiveness in terms of drug uptake and targeting. Human macrophages were loaded with iron oxide nanoparticles and different therapeutic agents: a chemotherapeutic agent (doxorubicin), tissue-plasminogen activator (t-PA) and two photosensitizers (disulfonated tetraphenyl chlorin-TPCS2a and 5,10,15,20-tetra(m-hydroxyphenyl)chlorin-mTHPC). The hybrid cell microvesicles were magnetically responsive, readily manipulated by magnetic forces and MRI-detectable. Using photosensitizer-loaded vesicles, we showed that the uptake of microvesicles by cancer cells could be kinetically modulated and spatially controlled under magnetic field and that cancer cell death was enhanced by the magnetic targeting. From the clinical editor: In this article, the authors devised a biogenic method using macrophages to produce microvesicles containing both iron oxide and chemotherapeutic agents. They showed that the microvesicles could be manipulated by magnetic force for targeting and subsequent delivery of the drug payload against cancer cells. This smart method could provide a novel way for future fight against cancer.
Assuntos
Antibióticos Antineoplásicos , Micropartículas Derivadas de Células/química , Doxorrubicina , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/química , Neoplasias/tratamento farmacológico , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/química , Doxorrubicina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Neoplasias/metabolismo , Neoplasias/patologiaRESUMO
Understanding the relation between the structure and the reactivity of nanomaterials in the organism is a crucial step towards efficient and safe biomedical applications. The multi-scale approach reported here, allows following the magnetic and structural transformations of multicore maghemite nanoflowers in a medium mimicking intracellular lysosomal environment. By confronting atomic-scale and macroscopic information on the biodegradation of these complex nanostuctures, we can unravel the mechanisms involved in the critical alterations of their hyperthermic power and their Magnetic Resonance imaging T1 and T2 contrast effect. This transformation of multicore nanoparticles with outstanding magnetic properties into poorly magnetic single core clusters highlights the harmful influence of cellular medium on the therapeutic and diagnosis effectiveness of iron oxide-based nanomaterials. As biodegradation occurs through surface reactivity mechanism, we demonstrate that the inert activity of gold nanoshells can be exploited to protect iron oxide nanostructures. Such inorganic nanoshields could be a relevant strategy to modulate the degradability and ultimately the long term fate of nanomaterials in the organism.
Assuntos
Biodegradação Ambiental , Compostos Férricos/química , Ouro/química , Nanoestruturas , Imageamento por Ressonância Magnética , Microscopia Eletrônica de TransmissãoRESUMO
As the conversion rate of preclinical studies for cancer treatment is low, user-friendly models that mimic the pathological microenvironment and drug intake with high throughput are scarce. Animal models are key, but an alternative to reduce their use would be valuable. Vascularized tumor-on-chip models combine great versatility with scalable throughput and are easy to use. Several strategies to integrate both tumor and vascular compartments have been developed, but few have been used to assess drug delivery. Permeability, intra/extravasation, and free drug circulation are often evaluated, but imperfectly recapitulate the processes at stake. Indeed, tumor targeting and chemoresistance bypass must be investigated to design promising cancer therapeutics. In vitro models that would help the development of drug delivery systems (DDS) are thus needed. They would allow selecting good candidates before animal studies based on rational criteria such as drug accumulation, diffusion in the tumor, and potency, as well as absence of side damage. In this review, we focus on vascularized tumor models. First, we detail their fabrication, and especially the materials, cell types, and coculture used. Then, the different strategies of vascularization are described along with their classical applications in intra/extravasation or free drug assessment. Finally, current trends in DDS for cancer are discussed with an overview of the current efforts in the domain.
Assuntos
Sistemas de Liberação de Medicamentos , Neoplasias , Humanos , Animais , Neoplasias/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Neovascularização Patológica/tratamento farmacológico , Microambiente Tumoral/efeitos dos fármacosRESUMO
Magnetomicelles were produced by the self-assembly of magnetite iron oxide nanoflowers and the amphiphilic poly(styrene)-b-poly(acrylic acid) block copolymer to deliver a multifunctional theranostic agent. Their bioprocessing by cancer cells was investigated in a three-dimensional spheroid model over a 13-day period and compared with nonencapsulated magnetic nanoflowers. A degradation process was identified and monitored at various scales, exploiting different physicochemical fingerprints. At a collective level, measurements were conducted using magnetic, photothermal, and magnetic resonance imaging techniques. At the nanoscale, transmission electron microscopy was employed to identify the morphological integrity of the structures, and X-ray absorption spectroscopy was used to analyze the degradation at the crystalline phase and chemical levels. All of these measurements converge to demonstrate that the encapsulation of magnetic nanoparticles in micelles effectively mitigates their degradation compared to individual nonencapsulated magnetic nanoflowers. This protective effect consequently resulted in better maintenance of their therapeutic photothermal potential. The structural degradation of magnetomicelles occurred through the formation of an oxidized iron phase in ferritin from the magnetic nanoparticles, leaving behind empty spherical polymeric ghost shells. These results underscore the significance of encapsulation of iron oxides in micelles in preserving nanomaterial integrity and regulating degradation, even under challenging physicochemical conditions within cancer cells.
Assuntos
Nanopartículas de Magnetita , Micelas , Poliestirenos , Humanos , Nanopartículas de Magnetita/química , Poliestirenos/química , Resinas Acrílicas/química , Linhagem Celular Tumoral , Óxido Ferroso-Férrico/química , AcrilatosRESUMO
INTRODUCTION: Despite considerable therapeutic advances in the last 20 years, metastatic cancers remain a major cause of death. We previously identified prominin-2 (PROM2) as a biomarker predictive of distant metastases and decreased survival, thus providing a promising bio-target. In this translational study, we set out to decipher the biological roles of PROM2 during the metastatic process and resistance to cell death, in particular for metastatic melanoma. METHODS AND RESULTS: Methods and results: We demonstrated that PROM2 overexpression was closely linked to an increased metastatic potential through the increase of epithelial-to-mesenchymal transition (EMT) marker expression and ferroptosis resistance. This was also found in renal cell carcinoma and triple negative breast cancer patient-derived xenograft models. Using an oligonucleotide anti-sense anti-PROM2, we efficaciously decreased PROM2 expression and prevented metastases in melanoma xenografts. We also demonstrated that PROM2 was implicated in an aggravation loop, contributing to increase the metastatic burden both in murine metastatic models and in patients with metastatic melanoma. The metastatic burden is closely linked to PROM2 expression through the expression of EMT markers and ferroptosis cell death resistance in a deterioration loop. CONCLUSION: Our results open the way for further studies using PROM2 as a bio-target in resort situations in human metastatic melanoma and also in other cancer types.
Assuntos
Ferroptose , Melanoma , Humanos , Animais , Camundongos , Ferroptose/genética , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/genética , Glicoproteínas de MembranaRESUMO
BACKGROUND INFORMATION: ATP is the main transmitter stored and released from astrocytes under physiological and pathological conditions. Morphological and functional evidence suggest that besides secretory granules, secretory lysosomes release ATP. However, the molecular mechanisms involved in astrocytic lysosome fusion remain still unknown. RESULTS: In the present study, we identify tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP, also called VAMP7) as the vesicular SNARE which mediates secretory lysosome exocytosis, contributing to release of both ATP and cathepsin B from glial cells. We also demonstrate that fusion of secretory lysosomes is triggered by slow and locally restricted calcium elevations, distinct from calcium spikes which induce the fusion of glutamate-containing clear vesicles. Downregulation of TI-VAMP/VAMP7 expression inhibited the fusion of ATP-storing vesicles and ATP-mediated calcium wave propagation. TI-VAMP/VAMP7 downregulation also significantly reduced secretion of cathepsin B from glioma. CONCLUSIONS: Given that sustained ATP release from glia upon injury greatly contributes to secondary brain damage and cathepsin B plays a critical role in glioma dissemination, TI-VAMP silencing can represent a novel strategy to control lysosome fusion in pathological conditions.
Assuntos
Trifosfato de Adenosina/metabolismo , Astrócitos/metabolismo , Cálcio/metabolismo , Catepsina B/metabolismo , Lisossomos/metabolismo , Proteínas R-SNARE/metabolismo , Animais , Astrócitos/citologia , Córtex Cerebral/citologia , Córtex Cerebral/embriologia , Córtex Cerebral/metabolismo , Regulação para Baixo , Embrião de Mamíferos , Exocitose , Glioma/metabolismo , Glioma/patologia , Hipocampo/citologia , Hipocampo/embriologia , Hipocampo/metabolismo , Humanos , Fusão de Membrana , Neuroglia/citologia , Neuroglia/metabolismo , Cultura Primária de Células , Ligação Proteica , Proteínas R-SNARE/antagonistas & inibidores , Proteínas R-SNARE/genética , RNA Interferente Pequeno/genética , Ratos , Transdução de Sinais , TransfecçãoRESUMO
This tutorial describes a method of controlled cell labeling with citrate-coated ultra small superparamagnetic iron oxide nanoparticles. This method may provide basically all kinds of cells with sufficient magnetization to allow cell detection by high-resolution magnetic resonance imaging (MRI) and to enable potential magnetic manipulation. In order to efficiently exploit labeled cells, quantify the magnetic load and deliver or follow-up magnetic cells, we herein describe the main requirements that should be applied during the labeling procedure. Moreover we present some recommendations for cell detection and quantification by MRI and detail magnetic guiding on some real-case studies in vitro and in vivo.
Assuntos
Espectroscopia de Ressonância Magnética/métodos , Nanopartículas de Magnetita/química , Imagem Molecular/métodos , Análise de Célula Única/métodos , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Contraste/química , Humanos , Nanopartículas de Magnetita/toxicidade , CamundongosRESUMO
The fate of carbon nanotubes in the organism is still controversial. Here, we propose a statistical high-throughput imaging method to localize and quantify functionalized multiwalled carbon nanotubes in cells. We give the first experimental evidence of an intercellular translocation of carbon nanotubes. This stress-induced longitudinal transfer of nanomaterials is mediated by cell-released microvesicles known as vectors for intercellular communication. This finding raises new critical issues for nanotoxicology, since carbon nanotubes could be disseminated by circulating extracellular cell-released vesicles and visiting several cells in the course of their passage into the organism.
Assuntos
Citometria de Fluxo/métodos , Imagem Molecular/métodos , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Frações Subcelulares/química , Frações Subcelulares/ultraestrutura , Células Cultivadas , Difusão , HumanosRESUMO
Engineered 3D brain-like models have advanced the understanding of neurological mechanisms and disease, yet their mechanical signature, while fundamental for brain function, remains understudied. The surface tension for instance controls brain development and is a marker of cell-cell interactions. Here, 3D magnetic brain-like tissue spheroids composed of intermixed primary glial and neuronal cells at different ratios are engineered. Remarkably, the two cell types self-assemble into a functional tissue, with the sorting of the neuronal cells toward the periphery of the spheroids, whereas the glial cells constitute the core. The magnetic fingerprint of the spheroids then allows their deformation when placed under a magnetic field gradient, at a force equivalent to a 70 g increased gravity at the spheroid level. The tissue surface tension and elasticity can be directly inferred from the resulting deformation, revealing a transitional dependence on the glia/neuron ratio, with the surface tension of neuronal tissue being much lower. The results suggest an underlying mechanical contribution to the exclusion of the neurons toward the outer spheroid region, and depict the glia/neuron organization as a sophisticated mechanism that should in turn influence tissue development and homeostasis relevant in the neuroengineering field.
Assuntos
Neuroglia , Neurônios , Tensão Superficial , Encéfalo , Movimento CelularRESUMO
With their distinctive physicochemical features, nanoparticles have gained recognition as effective multifunctional tools for biomedical applications, with designs and compositions tailored for specific uses. Notably, magnetic nanoparticles stand out as first-in-class examples of multiple modalities provided by the iron-based composition. They have long been exploited as contrast agents for magnetic resonance imaging (MRI) or as anti-cancer agents generating therapeutic hyperthermia through high-frequency magnetic field application, known as magnetic hyperthermia (MHT). This review focuses on two more recent applications in oncology using iron-based nanomaterials: photothermal therapy (PTT) and ferroptosis. In PTT, the iron oxide core responds to a near-infrared (NIR) excitation and generates heat in its surrounding area, rivaling the efficiency of plasmonic gold-standard nanoparticles. This opens up the possibility of a dual MHT + PTT approach using a single nanomaterial. Moreover, the iron composition of magnetic nanoparticles can be harnessed as a chemotherapeutic asset. Degradation in the intracellular environment triggers the release of iron ions, which can stimulate the production of reactive oxygen species (ROS) and induce cancer cell death through ferroptosis. Consequently, this review emphasizes these emerging physical and chemical approaches for anti-cancer therapy facilitated by magnetic nanoparticles, combining all-in-one functionalities.