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1.
Colloids Surf B Biointerfaces ; 235: 113788, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335770

RESUMO

Surface modification of lipid nanocapsules (LNC) is necessary to impart stealth properties to these drug carriers and enhance their accumulation into the tumor microenvironment. While pegylation is commonly used to prolong the circulation time of LNC, the increased presence of anti-PEG antibodies in the human population and the internalization issues associated to the PEG shell are strong incentives to search alternatives. This work describes the development of amphiphilic poly(N-vinyl amide)-based (co)polymers, including pH-responsive ones, and their use as LNC modifiers towards improved drug delivery systems. RAFT polymerization gave access to a series of LNC modifiers composed of poly(N-methyl-N-vinyl acetamide), poly(N-vinyl pyrrolidone) or pH-responsive vinylimidazole-based sequence bearing a variety of lipophilic end-groups, namely octadecyl, dioctadecyl or phospholipid groups, for anchoring to the LNC. Decoration of the LNC with these families of poly(N-vinyl amide) derivatives was achieved via both post-insertion and per-formulation methods. This offered valuable and non-toxic LNC protection from opsonization by complement activation, emphasized the benefit of dioctadecyl in the per-formulation approach and highlighted the great potential of poly(N-methyl-N-vinyl acetamide) as PEG alternative. Moreover, incorporation of imidazole moieties in the shell of the carrier imparted pH-responsiveness to the LNC likely to increase the cellular uptake in the acidic tumor microenvironment, opening up new possibilities in the field of active targeting.


Assuntos
Nanocápsulas , Humanos , Portadores de Fármacos , Fosfolipídeos , Concentração de Íons de Hidrogênio , Acetamidas , Amidas
2.
J Control Release ; 364: 700-717, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37951474

RESUMO

Nanoemulsions are metastable emulsions in the nanometric range which can be obtained using low-energy processes. A decade ago, it was demonstrated that a non-negligible amount of residual surfactant micelles may coexist with the oil nanodroplets in a model oil/surfactant system. Those micelles were called "wasted" micelles as they did not participate in the formation of the nanodroplets. Little attention has been focused on the potential presence or effect of such secondary structures in nanoemulsions used as drug delivery systems. Here, we present an extensive characterization of lipid nanocapsules, a nanoemulsion obtained from a medium-chain triglyceride mixed with a pegylated surfactant by a process comprising a temperature-dependent phase inversion followed by a cold-water quench. Lipid nanocapsules demonstrate a very good shelf stability. First, for clarity and academic purposes, we briefly present the pros and the cons of the various diffusion-based characterization techniques used i.e., multi-angle and single-angle dynamic light scattering, nanoparticle tracking analysis, fluorescence recovery after photobleaching, and diffusometry nuclear magnetic resonance. Then, combining all these techniques, we show that up to 40 wt% of the surfactant is not involved in the lipid nanocapsule construction but forms residual micellar structures. Those micelles also contain a small quantity of medium-chain triglyceride (2 wt% of the initial amount) and encapsulate around 40 wt% of a fluorescent dye originally dispersed in the oily phase.


Assuntos
Micelas , Nanocápsulas , Emulsões/química , Tensoativos/química , Triglicerídeos
3.
MAGMA ; 35(6): 1021-1029, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35552915

RESUMO

PURPOSE: This study aims at evaluating the non-invasive Magnetic Resonance Imaging (MRI) technic to visualize a synthetic composite hernia mesh using a rodent model and to document the integration of this device over 4 months. METHODS: Uncoated polyethylene terephthalate mesh and synthetic composite mesh-faced on the visceral side with a chemically engineered layer of copolymer of glycolide, caprolactone, trimethylene carbonate, and lactide to minimize tissue attachment-were placed intraperitoneally in rats, facing the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Meshes fate follow-up was performed 4, 10, and 16-weeks post-implantation using a rodent dedicated high field MRI. Magnetization transfer (MT) images were acquired, associated with pneumoperitonealMRI performed after intraperitoneal injection of 8 mL gas to induce mechanical stress on the abdominal wall. RESULTS: Uncoated meshes were clearly visible using both T2-weighted and MT imaging during the whole study while composite meshes conspicuity was not so evident on T2-weighted MRI and could be improved using MT imaging. Adhesions and collagen infiltration were massive for the uncoated meshes as expected. On the contrary, composite meshes showed very limited adhesion, and, if any, occurring at the edge of the mesh, starting at the fixation points. CONCLUSIONS: Magnetization transfer imaging allows to detect mesh integration and, associated with pneumoperitoneum, was able to probe the effective minimizing effect of the synthetic polymeric barrier on visceral attachments. However, magnetization transfer imaging could not unambiguously allow the visualization of the mesh through the polymeric barrier.


Assuntos
Hérnia Ventral , Ratos , Animais , Hérnia Ventral/cirurgia , Telas Cirúrgicas , Projetos Piloto , Polietilenotereftalatos , Seguimentos , Aderências Teciduais/patologia , Imageamento por Ressonância Magnética/métodos , Colágeno
4.
Nanomedicine (Lond) ; 16(28): 2539-2536, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34814704

RESUMO

To understand how nanoparticles (NPs) interact with biological barriers and to ensure they maintain their integrity over time, it is crucial to study their in vivo pharmacokinetic (PK) profiles. Many methods of tracking have been used to describe the in vivo fate of NPs and to evaluate their PKs and structural integrity. However, they do not deliver the same level of information and this may cause misinterpretations. Here, the authors review and discuss the different methods for in vivo tracking of organic NPs. Among them, Förster resonance energy transfer (FRET) presents great potential to track NPs' integrity. However, FRET still requires validated methods to extract and quantify NPs in biological fluids and tissues.


Assuntos
Nanopartículas , Transferência Ressonante de Energia de Fluorescência/métodos , Nanopartículas/química
5.
Biomater Sci ; 9(18): 6203-6213, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34350906

RESUMO

There is a growing interest in magnetic nanocomposites in biomaterials science. In particular, nanocomposites that combine poly(lactide) (PLA) nanofibers and superparamagnetic iron oxide nanoparticles (SPIONs), which can be obtained by either electrospinning of a SPION suspension in PLA or by precipitating SPIONs at the surface of PLA, are well documented in the literature. However, these two classical processes yield nanocomposites with altered materials properties, and their long-term in vivo fate and performances have in most cases only been evaluated over short periods of time. Recently, we reported a new strategy to prepare well-defined PLA@SPION nanofibers with a quasi-monolayer of SPIONs anchored at the surface of PLA electrospun fibers. Herein, we report on a 6-month in vivo rat implantation study with the aim of evaluating the long-term magnetic resonance imaging (MRI) properties of this new class of magnetic nanocomposites, as well as their tissue integration and degradation. Using clinically relevant T2-weighted MRI conditions, we show that the PLA@SPION nanocomposites are clearly visible up to 6 months. We also evaluate here by histological analyses the slow degradation of the PLA@SPIONs, as well as their biocompatibility. Overall, these results make these nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.


Assuntos
Nanopartículas de Magnetita , Nanocompostos , Animais , Nanopartículas Magnéticas de Óxido de Ferro , Imageamento por Ressonância Magnética , Poliésteres , Ratos
6.
J Control Release ; 337: 155-167, 2021 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-34280413

RESUMO

Nuclear Magnetic Resonance (NMR) based diffusion methods open new perspectives for nanomedicine characterization and their bioenvironment interaction understanding. This review summarizes the theoretical background of diffusion phenomena. Self-diffusion and mutual diffusion coefficient notions are featured. Principles, advantages, drawbacks, and key challenges of NMR diffusometry spectroscopic and imaging methods are presented. This review article also gives an overview of representative applicative works to the nanomedicine field that can contribute to elucidate important issues. Examples of in vitro characterizations such as identification of formulated species, process monitoring, drug release follow-up, nanomedicine interactions with biological barriers are presented as well as possible transpositions for studying in vivo nanomedicine fate.


Assuntos
Imageamento por Ressonância Magnética , Nanomedicina , Difusão , Imagem de Difusão por Ressonância Magnética , Espectroscopia de Ressonância Magnética
7.
Cancers (Basel) ; 12(4)2020 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-32290283

RESUMO

Recent findings suggest that S100A4, a protein involved in communication between stromal cells and cancer cells, could be more involved than previously expected in cancer invasiveness. To investigate its cumulative value in the multistep process of the pathogenesis of malignant mesothelioma (MM), SWATH-MS (sequential window acquisition of all theoretical fragmentation spectra), an advanced and robust technique of quantitative proteomics, was used to analyze a collection of 26 preneoplastic and neoplastic rat mesothelial cell lines and models of MM with increasing invasiveness. Secondly, proteomic and histological analyses were conducted on formalin-fixed paraffin-embedded sections of liver metastases vs. primary tumor, and spleen from tumor-bearing rats vs. controls in the most invasive MM model. We found that S100A4, along with 12 other biomarkers, differentiated neoplastic from preneoplastic mesothelial cell lines, and invasive vs. non-invasive tumor cells in vitro, and MM tumors in vivo. Additionally, S100A4 was the only protein differentiating preneoplastic mesothelial cell lines with sarcomatoid vs. epithelioid morphology in relation to EMT (epithelial-to-mesenchymal transition). Finally, S100A4 was the most significantly increased biomarker in liver metastases vs. primary tumor, and in the spleen colonized by MM cells. Overall, we showed that S100A4 was the only protein that showed increased abundance in all situations, highlighting its crucial role in all stages of MM pathogenesis.

8.
J Phys Chem Lett ; 10(21): 6613-6620, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31609118

RESUMO

The design of a simple platform to target the delivery of notably hydrophobic drugs into cancer cells is an ultimate goal. Here, three strategies were combined in the same nanovector, in limiting the use of excipients: cell-penetrating peptides, an amphiphilic prodrug, and self-assembly. Light scattering and cryogenic transmission electron microscopy revealed one size population of objects around 100 nm with a narrow size distribution. However, in-depth analysis of the suspension by nanoparticle tracking analysis, small-angle X-ray scattering, and nuclear magnetic resonance (NMR) diffusometry demonstrated the presence of another population of small objects (<2 nm). It has been shown that these small self-assemblies represented >99% of the matter! This presence was clearly and unambiguously demonstrated by NMR diffusometry experiments. The study highlights the importance and the complementary contribution of each characterization method to reflect the reality of the studied nanoassembly.


Assuntos
Peptídeos Penetradores de Células/química , Compostos Ferrosos/química , Células A549 , Peptídeos Penetradores de Células/metabolismo , Microscopia Crioeletrônica , Compostos Ferrosos/metabolismo , Humanos , Espectroscopia de Ressonância Magnética , Nanoestruturas/química , Tamanho da Partícula , Espalhamento a Baixo Ângulo , Difração de Raios X
9.
Mater Sci Eng C Mater Biol Appl ; 101: 396-403, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029333

RESUMO

Hypoxia is common occurrence of the tumour microenvironment, wherein heterogeneous gradients of O2 give rise to tumoural cells which are highly malignant, metastatic, and resistant to therapeutic efforts. Thus, the assessment and imaging of hypoxia is essential for tumour diagnosis and treatment. Magnetic resonance imaging and, more specifically, the quantitative assessment of longitudinal relaxation time enhancement, was shown to enable the mapping of oxygen in tumours with increased sensitivity for lipids as compared to water signal. Unfortunately, this can only be applied to tumours with high lipid content. To overcome this issue, we propose the use of lipid nanocapsules (LNCs). LNCs have been demonstrated as excellent core-shell nanocarriers, wherein the lipidic-core is used for lipophilic drug encapsulation, enabling treatment of highly malignant tumours. Herein, however, we exploited the lipidic-core of the LNCs to develop a simple but effective technique to increase the lipidic content within tissues to enable the assessment and mapping of pO2. LNCs were prepared using the phase-inversion technique to produce 60 nm sized nanoparticles, and in vitro studies demonstrated the permeability and responsiveness of LNCs to O2. To evaluate the ability of LNCs to respond to changes in pO2in vivo, after a hyperoxic challenge, three animal models, namely a normal tissue model (gastrocnemius muscle tissue) and two tumour tissue models (subcutaneous fibrosarcoma and intracerebral glioblastoma) were explored. LNCs were found to be responsive to variation of O2in vivo. Moreover, the use of MRI enabled the mapping of oxygen gradients and heterogeneity within tumours.


Assuntos
Lipídeos/química , Imageamento por Ressonância Magnética , Nanocápsulas/química , Oxigênio/análise , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Glioblastoma/patologia , Masculino , Camundongos , Pressão Parcial , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
10.
ACS Appl Mater Interfaces ; 11(9): 9519-9529, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30729776

RESUMO

Composites combining superparamagnetic iron oxide nanoparticles (SPIONs) and polymers are largely present in modern (bio)materials. However, although SPIONs embedded in polymer matrices are classically reported, the mechanical and degradation properties of the polymer scaffold are impacted by the SPIONs. Therefore, the controlled anchoring of SPIONs onto polymer surfaces is still a major challenge. Herein, we propose an efficient strategy for the direct and uniform anchoring of SPIONs on the surface of functionalized-polylactide (PLA) nanofibers via a simple free ligand exchange procedure to design PLA@SPIONs core@shell nanocomposites. The resulting PLA@SPIONs hybrid biomaterials are characterized by electron microscopy (scanning electron microscopy and transmission electron microscopy) and energy-dispersive X-ray spectroscopy analysis to probe the morphology and detect elements present at the organic-inorganic interface, respectively. A monolayer of SPIONs with a complete and homogeneous coverage is observed on the surface of PLA nanofibers. Magnetization experiments show that magnetic properties of the nanoparticles are well preserved after their grafting on the PLA fibers and that the size of the nanoparticles does not change. The absence of cytotoxicity, combined with a high sensitivity of detection in magnetic resonance imaging both in vitro and in vivo, makes these hybrid nanocomposites attractive for the development of magnetic biomaterials for biomedical applications.

11.
Acta Biomater ; 84: 268-279, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30465922

RESUMO

Glioblastoma (GB) is a highly infiltrative tumor, recurring, in 90% of cases, within a few centimeters of the surgical resection cavity, even with adjuvant chemo/radiotherapy. Residual GB cells left in the margins or infiltrating the brain parenchyma shelter behind the extremely fragile and sensitive brain tissue and may favor recurrence. Tools for eliminating these cells without damaging the brain microenvironment are urgently required. We propose a strategy involving the implantation, into the tumor bed after resection, of a scaffold to concentrate and trap these cells, to facilitate their destruction by targeted therapies, such as stereotactic radiosurgery. We used bacterial cellulose (BC), an easily synthesized and modifiable random nanofibrous biomaterial, to make the trap. We showed that the structure of BC membranes was ideal for trapping tumor cells and that BC implants were biocompatible with brain parenchyma. We also demonstrated the visibility of BC on magnetic resonance imaging, making it possible to follow its fate in clinical situations and to define the target volume for stereotactic radiosurgery more precisely. Furthermore, BC membranes can be loaded with chemoattractants, which were released and attracted tumor cells in vitro. This is of particular interest for trapping GB cells infiltrating tissues within a few centimeters of the resection cavity. Our data suggest that BC membranes could be a scaffold of choice for implantation after surgical resection to trap residual GB cells. STATEMENT OF SIGNIFICANCE: Glioblastoma is a highly infiltrative tumor, recurring, in 90% of cases, within a few centimeters of the surgical resection cavity, even with adjuvant chemo/radiotherapy. Residual tumor cells left in the margins or infiltrating the brain parenchyma shelter behind the extremely fragile and sensitive brain tissue and contribute to the risk of recurrence. Finding tools to eliminate these cells without damaging the brain microenvironment is a real challenge. We propose a strategy involving the implantation, into the walls of the surgical resection cavity, of a scaffold to concentrate and trap the residual tumor cells, to facilitate their destruction by targeted therapies, such as stereotactic radiosurgery.


Assuntos
Materiais Biocompatíveis , Neoplasias Encefálicas , Glioblastoma , Imageamento por Ressonância Magnética , Membranas Artificiais , Nanofibras , Radiocirurgia , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/radioterapia , Linhagem Celular Tumoral , Celulose/química , Celulose/uso terapêutico , Glioblastoma/diagnóstico por imagem , Glioblastoma/metabolismo , Glioblastoma/radioterapia , Humanos , Masculino , Nanofibras/química , Nanofibras/uso terapêutico , Ratos , Ratos Sprague-Dawley , Microambiente Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos da radiação
12.
ACS Appl Mater Interfaces ; 11(1): 403-416, 2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30541280

RESUMO

Noninvasive diagnostic by imaging combined with a contrast agent (CA) is by now the most used technique to get insight into human bodies. X-ray and magnetic resonance imaging (MRI) are widely used technologies providing complementary results. Nowadays, it seems clear that bimodal CAs could be an emerging approach to increase the patient compliance, accessing different imaging modalities with a single CA injection. Owing to versatile designs, targeting properties, and high payload capacity, nanocarriers are considered as a viable solution to reach this goal. In this study, we investigated efficient superparamagnetic iron oxide nanoparticle (SPION)-loaded iodinated nano-emulsions (NEs) as dual modal injectable CAs for X-ray imaging and MRI. The strength of this new CA lies not only in its dual modal contrasting properties and biocompatibility, but also in the simplicity of the nanoparticulate assembling: iodinated oily core was synthesized by the triiodo-benzene group grafting on vitamin E (41.7% of iodine) via esterification, and SPIONs were produced by thermal decomposition during 2, 4, and 6 h to generate SPIONs with different morphologies and magnetic properties. SPIONs with most anisotropic shape and characterized by the highest r2/ r1 ratio once encapsulated into iodinated NE were used for animal experimentation. The in vivo investigation showed an excellent contrast modification because of the presence of the selected NEs, for both imaging techniques explored, that is, MRI and X-ray imaging. This work provides the description and in vivo application of a simple and efficient nanoparticulate system capable of enhancing contrast for both preclinical imaging modalities, MRI, and computed tomography.


Assuntos
Meios de Contraste , Iodo , Imageamento por Ressonância Magnética/métodos , Nanopartículas de Magnetita , Tomografia Computadorizada por Raios X/métodos , Animais , Meios de Contraste/química , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Emulsões , Células HeLa , Humanos , Iodo/química , Iodo/farmacocinética , Iodo/farmacologia , Nanopartículas de Magnetita/química , Nanopartículas de Magnetita/uso terapêutico , Camundongos
13.
Nanomedicine (Lond) ; 13(16): 1999-2013, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30204064

RESUMO

AIM: Anticancer drug-loaded hydrogels are a promising strategy for the local treatment of incurable brain tumors such as glioblastoma (GBM). Recently, we demonstrated the efficacy of lauroyl-gemcitabine lipid nanocapsule hydrogel (GemC12-LNC) in a U-87 MG xenograft orthotopic mouse model. In this study, we developed a reliable and reproducible surgical procedure to resect orthotopic GBM tumors in rats. GemC12-LNC hydrogel integrity was tested after brain administration in rats and its anti-tumor efficacy was tested on a 9L syngeneic orthotopic model. RESULTS: We demonstrated that LNC integrity is maintained at least for one week after local administration of GemC12-LNC. GemC12-LNC was able to delay the formation of recurrences in 9L tumor-bearing resected rats, demonstrating the efficacy of this nanomedicine hydrogel in this preclinical model. CONCLUSION: Our results confirm that GemC12-LNC, a hydrogel uniquely formed by a nanocarrier and a cytotoxic drug, could be a promising and safe delivery tool for the local treatment of operable GBM tumors.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Glioblastoma/tratamento farmacológico , Hidrogéis/química , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Desoxicitidina/administração & dosagem , Desoxicitidina/química , Desoxicitidina/uso terapêutico , Feminino , Imageamento por Ressonância Magnética , Nanomedicina/métodos , Ratos , Ratos Sprague-Dawley , Gencitabina
14.
Magn Reson Med ; 79(4): 1981-1991, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28833514

RESUMO

PURPOSE: To propose a method for determining tissue oxygenation via the measurement of fat T1 . The method is based on a 2D fat/water chemical shift-encoded and T1 -weighted acquisition. THEORY AND METHODS: A 2D data set was acquired with a fast spin echo sequence with several echo asymmetries and repetition times, wherein one dimension is related to the fat/water phase modulation and the other to the T1 saturation recovery. A joint magnitude-based process of phase modulation and T1 evolution allowed for the collection of the fat fraction and T1 maps with resolved fat or water dominance ambiguity while avoiding the phased error problem. RESULTS: In vitro imaging allowed for the attribution of fat content for different water/oil emulsions that demonstrated longitudinal relaxation rate (R1 ) sensitivity to the oxygenated emulsion environment. The fat R1 values were subsequently compared to reference values, which were measured using low receiver bandwidth acquisition to enhance water and fat signal separations. In vivo feasibility of tissue oxygenation assessment was demonstrated by investigating interscapular brown adipose tissue modifications during an air/carbogen challenge in rats. CONCLUSION: The proposed method offers a precise and robust estimate of tissue oxygenation illustrated by the method's ability to detect-brown adipose tissue oxygenation modifications. Magn Reson Med 79:1981-1991, 2018. © 2017 International Society for Magnetic Resonance in Medicine.


Assuntos
Tecido Adiposo Marrom/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Oxigênio/química , Animais , Dióxido de Carbono/química , Feminino , Análise dos Mínimos Quadrados , Modelos Estatísticos , Imagens de Fantasmas , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Água
15.
J Pharm Biomed Anal ; 148: 156-162, 2018 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-29031133

RESUMO

NMR diffusometry is a powerful but challenging method to analyze complex mixture. Each component diffuses differently, from the faster small species to the slower large species, corresponding to different signal attenuation. However, the method is highly sensitive to the quality of the acquired data and the performance of the processing used to resolve multiexponential signals influences. Adapting the signal decay sampling to the mixture composition is one way to improve the precision of the measure. In this work, we propose a prediction tool, based on the calculation of the Cramér-Rao lower bound to minimize the variance of diffusion coefficient estimation in order to determine the optimal number of diffusion gradient steps, the best diffusion gradient sampling (among linear, exponential, quadratic and sigmoidal ones) and the optimal maximum diffusion factor. The tool was validated experimentally on a unimer/micelle solution of sodium dodecyl sulfate and on Caelyx®, a commercial liposomal preparation containing a mixture of pegylated-liposomes and sucrose.


Assuntos
Soluções/análise , Soluções/química , Difusão , Doxorrubicina/análogos & derivados , Doxorrubicina/química , Lipossomos/química , Micelas , Ressonância Magnética Nuclear Biomolecular/métodos , Polietilenoglicóis/química , Dodecilsulfato de Sódio/química
16.
PLoS One ; 11(10): e0165479, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27788227

RESUMO

Growing tumor cell lines, such as U87-MG glioma cells, under mild hypoxia (3% O2) leads to a ca. 40% reduction in growth rate once implanted in the brain of nude mice, as compared to normoxia (21% O2) grown cells, wherein the former over-express HIF-1 and VEGF-A. Despite developing differently, the tumors have similar: blood perfusion, oxygen consumption, and vascular surface area parameters, whereas the number of blood vessels is nearly doubled in the tumor arising from normoxia cultured cells. Interestingly, tumor oxygen tension, measured using 19F-oximetry, showed that the normoxia grown cells led to tumors characterized by mild hypoxic environment (approximately 4%) conditions, whilst the hypoxia grown cells led to tumors characterized by physioxic environment (approximately 6%) conditions. This reversal in oxygen concentration may be responsible for the apparent paradoxical growth profiles.


Assuntos
Fluorocarbonos/química , Glioblastoma/metabolismo , Glioblastoma/patologia , Lipídeos/química , Nanocápsulas/química , Oxigênio/metabolismo , Animais , Atmosfera/química , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiopatologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Feminino , Glioblastoma/irrigação sanguínea , Glioblastoma/diagnóstico por imagem , Humanos , Camundongos , Oxigênio/farmacologia
17.
Int J Pharm ; 495(2): 972-80, 2015 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-26428632

RESUMO

In this work, multifunctional lipid nanocapsules (M-LNC) were designed to combine the activity of the cytotoxic drug paclitaxel (PTX) with the immunostimulant CpG. This nanosystem, consisting of modified lipid nanocapsules coated with a cationic polymeric shell composed of chitosan (CS), was able to allocate the hydrophobic drug PTX in the inner oily core, and to associate onto the surface the genetic material CpG. The CS-coated LNC (CS-LNC), showed a narrow size distribution with an average size of 70 nm and a positive zeta potential (+25 mV). They encapsulated PTX in a high amount (98%), and, due to the cationic surface charge, were able to adsorb CpG without losing stability. As a preliminary in vitro study, the apoptotic effect on GL261 glioma cells was investigated. The drug-loaded CS-LNC exhibited the ability to interact with glioma cells and induce an important apoptotic effect in comparison with blank systems. Finally, the M-LNC made of CS-LNC loaded with both CpG and PTX were tested in vivo, injected via convention enhanced delivery (CED) in GL261-glioma-bearing mice. The results showed that the overall survival of mice treated with the M-LNC was significantly increased in comparison with the control, Taxol(®), or the separated injection of PTX-loaded LNC and CpG. This effect was also confirmed by magnetic resonance imaging (MRI) which revealed the reduction of tumor growth in the animals treated with CpG and PTX-loaded M-LNC. All these findings suggested that the developed M-LNC could potentiate both CpG immunopotency and PTX antitumor activity by enhancing its delivery into the tumor microenvironment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Glioblastoma/tratamento farmacológico , Lipídeos/administração & dosagem , Nanocápsulas/administração & dosagem , Oligodesoxirribonucleotídeos/administração & dosagem , Oligodesoxirribonucleotídeos/farmacologia , Paclitaxel/administração & dosagem , Paclitaxel/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Quitosana/química , Ensaios de Seleção de Medicamentos Antitumorais , Estabilidade de Medicamentos , Feminino , Glioblastoma/metabolismo , Glioblastoma/patologia , Lipídeos/química , Imageamento por Ressonância Magnética , Camundongos , Nanocápsulas/química
18.
Plant Methods ; 11: 6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25694791

RESUMO

We review a set of recent multiscale imaging techniques, producing high-resolution images of interest for plant sciences. These techniques are promising because they match the multiscale structure of plants. However, the use of such high-resolution images is challenging in the perspective of their application to high-throughput phenotyping on large populations of plants, because of the memory cost for their data storage and the computational cost for their processing to extract information. We discuss how this renews the interest for multiscale image processing tools such as wavelets, fractals and recent variants to analyse such high-resolution images.

19.
Int J Nanomedicine ; 10: 1259-71, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25709447

RESUMO

Recently developed drug delivery nanosystems, such as lipid nanocapsules (LNCs), hold great promise for the treatment of glioblastomas (GBs). In this study, we used a subpopulation of human mesenchymal stem cells, "marrow-isolated adult multilineage inducible" (MIAMI) cells, which have endogenous tumor-homing activity, to deliver LNCs containing an organometallic complex (ferrociphenol or Fc-diOH), in the orthotopic U87MG GB model. We determined the optimal dose of Fc-diOH-LNCs that can be carried by MIAMI cells and compared the efficacy of Fc-diOH-LNC-loaded MIAMI cells with that of the free-standing Fc-diOH-LNC system. We showed that MIAMI cells entrapped an optimal dose of about 20 pg Fc-diOH per cell, with no effect on cell viability or migration capacity. The survival of U87MG-bearing mice was longer after the intratumoral injection of Fc-diOH-LNC-loaded MIAMI cells than after the injection of Fc-diOH-LNCs alone. The greater effect of the Fc-diOH-LNC-loaded MIAMI cells may be accounted for by their peritumoral distribution and a longer residence time of the drug within the tumor. These results confirm the potential of combinations of stem cell therapy and nanotechnology to improve the local tissue distribution of anticancer drugs in GB.


Assuntos
Antineoplásicos , Compostos Ferrosos , Glioblastoma/terapia , Lipídeos , Transplante de Células-Tronco Mesenquimais , Nanocápsulas , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Antineoplásicos/toxicidade , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Compostos Ferrosos/administração & dosagem , Compostos Ferrosos/química , Compostos Ferrosos/uso terapêutico , Compostos Ferrosos/toxicidade , Humanos , Lipídeos/administração & dosagem , Lipídeos/química , Lipídeos/uso terapêutico , Lipídeos/toxicidade , Camundongos , Nanocápsulas/administração & dosagem , Nanocápsulas/química , Nanocápsulas/uso terapêutico , Nanocápsulas/toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Surg Endosc ; 29(6): 1567-73, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25294530

RESUMO

BACKGROUND: Intraperitoneal mesh implantation is often associated with formation of adhesion to the mesh. This experimental study examines the potential of minimally invasive pneumoperitoneal-MRI to assess these adhesions in a preclinical context. METHODS: Uncoated polyethylene terephthalate meshes were placed intraperitoneally in rats, in regard to the caecum previously scraped to promote petechial bleeding and subsequent adhesions. Examinations were performed 2-weeks post mesh implantation using a rodent dedicated high field MRI. Respiratory-triggered T2-weighted images were acquired prior to and after intraperitoneal injection of ~8-10 mL gas to induce a mechanical stress on the abdominal wall. RESULTS: Adhesions are occasionally seen in sham-operated rats as opposed to rats receiving polyethylene terephthalate meshes. On high-resolution images, meshes can be detected due to their characteristic net shape. However, evidence of adherence is only found if intraperitoneal gas injection is performed, when a ~1-cm elevation of the abdominal wall is observed. When adherence occurs between the mesh and the caecum, the latter remains in contact with the wall. Looser adherences between visceral tissue and meshes are also observed. CONCLUSIONS: T2-weighted pneumoperitoneal-MRI is a powerful tool for assessing adherence after intraperitoneal mesh implantation. According to the mini-invasive procedure adopted here, this approach may allow a temporal follow-up of adherence fate.


Assuntos
Doenças do Ceco/patologia , Imageamento por Ressonância Magnética/métodos , Peritônio/cirurgia , Pneumoperitônio Artificial , Telas Cirúrgicas/efeitos adversos , Aderências Teciduais/patologia , Animais , Doenças do Ceco/etiologia , Ceco/cirurgia , Feminino , Polietilenotereftalatos , Polímeros , Ratos Sprague-Dawley , Aderências Teciduais/etiologia
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