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1.
J Magn Reson Imaging ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39228293

RESUMO

BACKGROUND: Intravenous Ferumoxtran-10 belongs to ultra-small superparamagnetic iron oxide particles and can be used for magnetic resonance neurography (MRN) as an alternative to other imaging methods which use contrast agents. PURPOSE: To examine the impact of intravenous Ferumoxtran-10 on vascular suppression and compare image quality to gadolinium (Gd)-enhanced image acquisition in MRN of lumbosacral plexus (LS). STUDY TYPE: Prospective. POPULATION/SUBJECTS: 17 patients with Ferumoxtran-10-enhanced MRN, and 20 patients with Gd-enhanced MRN. FIELDSTRENGTH/SEQUENCE: 3T/3D STIR sequence. ASSESSMENT: Image quality, nerve visibility and vascular suppression were evaluated by 3 readers using a 5-point Likert scale. STATISTICAL TESTS: Inter-reader agreement (IRA) was calculated using intraclass coefficients (ICC). Quantitative analysis of image quality was performed by signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) measurements and compared using Student's t-testing. RESULTS: Image quality, nerve visibility and vascular suppression were significantly higher for Ferumoxtran-10-enhanced MRN compared to Gd-enhanced MRN sequences (p < 0.05). IRA for image quality of nerves was good in Gd-enhanced and Ferumoxtran-10 MRN with ICC values of 0.76 and 0.89, respectively. IRA for nerve visibility was good in Gd- and Ferumoxtran-10 enhanced MR neurography (ICC 0.72 and 0.90). Mean SNR was significantly higher in Ferumoxtran-10-enhanced MRN for all analyzed structures, while mean CNR was for significantly better for S1 ganglion and femoral nerve in Ferumoxtran-10-enhanced MRN (p < 0.05). DATA CONCLUSION: Ferumoxtran-10-enhanced MRN of the LS plexus showed significantly higher image quality and nerve visibility with better vascular suppression as compared to Gd-enhanced MRN. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

2.
Front Pharmacol ; 15: 1433734, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246659

RESUMO

Introduction: The study aimed to systematically enhance the fabrication process of flurbiprofen-loaded bilosomes (FSB) using Quality by Design (QbD) principles and Design of Experiments (DOE). The objective was to develop an optimized formulation with improved entrapment efficiency and targeted drug delivery capabilities. Methods: The optimization process involved applying QbD principles and DOE to achieve the desired formulation characteristics. Superparamagnetic iron oxide nanoparticles (SPIONs) were incorporated to impart magnetic responsiveness. The size, entrapment efficiency, morphology, and in vitro release patterns of the FSB formulation were evaluated. Additionally, an in situ forming hydrogel incorporating FSB was developed, with its gelation time and drug release kinetics assessed. In vivo studies were conducted on osteoarthritic rats to evaluate the efficacy of the FSB-loaded hydrogel. Results: The optimized FSB formulation yielded particles with a size of 453.60 nm and an entrapment efficiency of 91.57%. The incorporation of SPIONs enhanced magnetic responsiveness. Morphological evaluations and in vitro release studies confirmed the structural integrity and sustained release characteristics of the FSB formulation. The in situ forming hydrogel exhibited a rapid gelation time of approximately 40 ± 1.8 s and controlled drug release kinetics. In vivo studies demonstrated a 27.83% reduction in joint inflammation and an 85% improvement in locomotor activity in osteoarthritic rats treated with FSB-loaded hydrogel. Discussion: This comprehensive investigation highlights the potential of FSB as a promising targeted drug delivery system for the effective management of osteoarthritis. The use of QbD and DOE in the formulation process, along with the integration of SPIONs, resulted in an optimized FSB formulation with enhanced entrapment efficiency and targeted delivery capabilities. The in situ forming hydrogel further supported the formulation's applicability for injectable applications, providing rapid gelation and sustained drug release. The in vivo results corroborate the formulation's efficacy, underscoring its potential for improving the treatment of osteoarthritis.

3.
Nanomedicine (Lond) ; : 1-15, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258568

RESUMO

Adoptive cell therapy (ACT) is on the horizon as a thrilling therapeutic plan for cancer. However, widespread application of ACT is often restricted by several challenges, including complexity of priming tumor-specific T cells and poor trafficking in solid tumors. The convergence of nanotechnology and cancer immunotherapy is coming of age and could address the limitations of ACT. Recent studies have provided evidence on the application of magnetic nanoparticles (MNPs) to generate smart immune cells and to bypass problems associated with conventional ACT. Herein, we review current progress in the application of MNPs to improve preparing, guiding and tracking immune cells in cancer ACT. Besides, we comment on the challenges ahead and strategies to optimize MNPs for clinical settings.


[Box: see text].

4.
Mater Today Bio ; 28: 101213, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39280110

RESUMO

An increasing number of medications have been explored to treat the progressive and irreversible Alzheimer's disease (AD) that stands as the predominant form of dementia among neurodegenerative ailments. However, assertions about toxic side effects of these drugs are a significant hurdle to overcome, calling for drug-free nanotherapeutics. Herein, a new therapeutic strategy devoid of conventional drugs or other cytotoxic species was developed. The constructed superparamagnetic iron oxide nanoparticles (SPIONs) nanospinners can accrete neurotoxic ß-amyloid 42 oligomers (oAß42) into aggregated magnetic plaques (mpAß) by mechanical rotating force via remote interaction between nanoparticles and the applied magnetic field. While the cellular uptake of mpAß attained from the magnetic stirring treatment by neuronal cells is severely limited, the facile phagocytic uptake of mpAß by microglial cells leads to the polarization of the brain macrophages to M2 phenotype and thus the increased anti-inflammatory responses to the treatment. The SPION stirring treatment protects the AD mice from memory deterioration and maintain cognitive ability as evidenced from both nesting and Barnes maze tests. The examination of the oAß42 injected brain tissues with the stirring treatment showed significant amelioration of functional impairment of neurons, microglia, astrocytes and oligodendrocytes alongside no obvious tissue damage caused by stirring meanwhile complete degradation of SPION was observed at day 7 after the treatment. The in vitro and animal data of this work strongly corroborate that this new modality of undruggable stirring treatment with SPIONs provides a new feasible strategy for developing novel AD treatments.

5.
Nanotoxicology ; : 1-16, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39275857

RESUMO

Inhalation exposure to iron oxide occurs in many workplaces and respirable aerosols occur during thermal processes (e.g. welding, casting) or during abrasion of iron and steel products (e.g. cutting, grinding, machining, polishing, sanding) or during handling of iron oxide pigments. There is limited evidence of adverse effects in humans specifically linked to inhalation of iron oxides. This contrasts to oxides of other metals used to alloy or for coating of steel and iron of which several have been classified as being hazardous by international and national agencies. Such metal oxides are often present in the air at workplaces. In general, iron oxides might therefore be regarded as low-toxicity, low-solubility (LTLS) particles, and are often considered to be nontoxic even if very high and prolonged inhalation exposures might result in diseases. In animal studies, such exposures lead to cancer, fibrosis and other diseases. Our hypothesis was that pulmonary-workplace exposure during manufacture and handling of SPION preparations might be harmful. We therefore conducted a systematic review of the relevant literature to understand how iron oxides deposited in the lung are related to acute and subchronic pulmonary inflammation. We included one human and several in vivo animal studies published up to February 2023. We found 25 relevant studies that were useful for deriving occupational exposure limits (OEL) for iron oxides based on an inflammatory reaction. Our review of the scientific literature indicates that lowering of health-based occupational exposure limits might be considered.

6.
J Psychiatr Res ; 179: 244-256, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39321523

RESUMO

Alzheimer's disease (AD) is a devastating kind of dementia that is becoming more common worldwide. Toxic amyloid-beta (Aß) aggregates are the primary cause of AD onset and development. Superparamagnetic iron oxide nanoparticles (SPIONs) have received a lot of interest in AD therapy over the last decade because of their ability to redirect the Aß fibrillation process and improve associated brain dysfunction. The potential diagnostic application of SPIONs in AD has dramatically increased this interest. Furthermore, surface-modified engineered SPIONs function as drug carriers to improve the efficacy of current therapies. Various preclinical and clinical studies on the role of SPIONs in AD pathology have produced encouraging results. However, due to their physicochemical properties (e.g., size, surface charge, and particle concentration) in the biological milieu, SPIONs may play the role of a preventive or accelerative agent in AD. Even though SPIONs are potential therapeutic and diagnostic options in AD, significant efforts are still needed to overcome the inconsistencies and safety concerns. This review evaluated the current understanding of how various SPIONs interact with AD models and explored the discrepancies in their efficacy and safety.

7.
Int J Med Sci ; 21(11): 2233-2243, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39239546

RESUMO

Purpose: Cognitive dysfunction caused by chronic cerebral hypoperfusion (CCH) is the leading cause of vascular dementia. Therefore, it is necessary to explore the mechanism that causes cerebral injury and find an effective therapy. Methods: Bone marrow mononuclear cells (BMMNCs) were extracted to detect the activity by CCK-8 kit and verify the transfection efficiency using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). A CCH rat model was established. Superparamagnetic iron oxide nanoparticles (BMPs)-PEI-Slit2/BMMNCs were injected into the tail vein and intervened with an external magnetic field. Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The Slit/Robo pathway-related proteins Slit2 and Robo4 were detected by RT-qPCR and Western blotting. Results: The neurological score of the CCH group significantly increased compared with that of the sham group (P<0.05). The levels of brain injury markers S-100ß and NSE were significantly higher in the CCH group than in the sham group (P<0.05). Neuronal apoptosis in the frontal cortex and hippocampus of CCH rats significantly increased compared with that of the sham group (P<0.05). The expression levels of Slit2 and Robo4 mRNAs and proteins in brain tissue of CCH rats significantly increased (P<0.05). The neurological function scores of CCH rats treated with BMP-PEI-Slit2/BMMNC significantly increased after Robo4 siRNA administration (P<0.05). Conclusion: BMP combination with the CCH-related gene Slit2 can effectively improve the efficiency of BMMNC transplantation in treatment.


Assuntos
Isquemia Encefálica , Disfunção Cognitiva , Modelos Animais de Doenças , Peptídeos e Proteínas de Sinalização Intercelular , Proteínas do Tecido Nervoso , Animais , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Ratos , Disfunção Cognitiva/terapia , Disfunção Cognitiva/etiologia , Isquemia Encefálica/terapia , Isquemia Encefálica/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Humanos , Masculino , Nanopartículas de Magnetita/administração & dosagem , Nanopartículas de Magnetita/química , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Células da Medula Óssea , Apoptose/genética , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Ratos Sprague-Dawley , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Terapia Genética/métodos , Proteínas Roundabout
8.
Small ; : e2406631, 2024 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-39205548

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted wide attention due to their promising applications in biomedicine, chemical catalysis, and magnetic memory devices. In this work, the force is measured between a single SPION coated with chiral molecules and a ferromagnetic substrate by atomic force microscopy (AFM), with the substrate magnetized either toward or away from the approaching AFM tip. The force between the coated SPION and the magnetic substrate depends on the handedness of the molecules adsorbed on the SPION and on the direction of the magnetization of the substrate. By inserting nm-scale spacing layers between the coated SPION and the magnetic substrate it is shown that the SPION has a short-range magnetic monopole-like magnetic field. A theoretical framework for the nature of this field is provided.

9.
Colloids Surf B Biointerfaces ; 244: 114141, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39216444

RESUMO

Lung cancer is among most prevalent cancers in the world, in which non-small cell lung cancer (NSCLC) accounts for more than 85 % of all subtypes of lung cancers. NSCLC is often diagnosed at an advanced stage with a high mortality rate. Despite the demonstrated efficacy of chemotherapy in the treatment of NSCLC, the main drawback of current therapy is the lack of an effective drug-targeted delivery system, which may result in undesirable side effects during the clinical treatment. In this study, we construct a "dual-targeting" anti-cancer drug delivery platform by combining superparamagnetic iron oxide nanoparticles (SPIONs) with exosomes derived from NSCLC cells. We successfully promoted the targeted delivery of anti-drug doxorubicin (DOX) at the cellular levels by combining the homing targeted ability of exosomes with the magnetic targeted ability of SPIONs. Moreover, non-small cell lung cancer cell (NCI-h1299) tumor models were established. It was found that exosome-SPIONs (Exo-SPIONs) loaded with DOX exhibited optimal tumor tissue delivery and tumor suppression in the presence of an external magnetic field, and reduced the toxicity of the DOX to normal tissues. The constructed "dual-targeting" anti-cancer drug delivery platform holds promise for targeted chemotherapy for NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Doxorrubicina , Sistemas de Liberação de Medicamentos , Exossomos , Neoplasias Pulmonares , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Exossomos/química , Exossomos/metabolismo , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Animais , Linhagem Celular Tumoral , Camundongos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , Proliferação de Células/efeitos dos fármacos , Nanopartículas Magnéticas de Óxido de Ferro/química , Sobrevivência Celular/efeitos dos fármacos , Camundongos Nus , Nanopartículas de Magnetita/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Endogâmicos BALB C , Ensaios de Seleção de Medicamentos Antitumorais
10.
Colloids Surf B Biointerfaces ; 241: 114051, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38954935

RESUMO

There has been a surge in effort in the development of various solid nanoparticles as Pickering emulsion stabilizers in the past decades. Regardless, the exploration of stabilizers that simultaneously stabilize and deliver bioactive has been limited. For this, liposomes with amphiphilic nature have been introduced as Pickering emulsion stabilizers but these nano-sized vesicles lack targeting specificity. Therefore in this study, superparamagnetic iron oxide nanoparticles (SPION) encapsulated within liposomes (MLP) were used as Pickering emulsion stabilizers to prepare pH and magnetic-responsive Pickering emulsions. A stable MLP-stabilized Pickering emulsion formulation was established by varying the MLP pH, concentration, and oil loading during the emulsification process. The primary stabilization mechanism of the emulsion under pH variation was identified to be largely associated with the MLP phosphate group deprotonation. When subjected to sequential pH adjustment to imitate the gastrointestinal digestion pH environment, a recovery in Pickering emulsion integrity was observed as the pH changes from acidic to alkaline. By incorporating SPION, the Pickering emulsion can be guided to the targeted site under the influence of a magnetic field without compromising emulsion stability. Overall, the results demonstrated the potential of MLP-stabilized Pickering emulsion as a dual pH- and magnetic-responsive drug delivery carrier with the ability to co-encapsulate hydrophobic and hydrophilic bioactive.


Assuntos
Emulsões , Lipossomos , Nanopartículas Magnéticas de Óxido de Ferro , Emulsões/química , Lipossomos/química , Concentração de Íons de Hidrogênio , Nanopartículas Magnéticas de Óxido de Ferro/química , Tamanho da Partícula , Nanopartículas de Magnetita/química
11.
Artigo em Inglês | MEDLINE | ID: mdl-39078330

RESUMO

There is a critical need for novel approaches to translate cell therapy and regenerative medicine to clinical practice. Magnetic cell targeting with site specificity has started to open avenues in these fields as a potential therapeutic platform. Magnetic targeting is gaining popularity in the field of biomedicine due to its ability to concentrate and retain at a target site while minimizing deleterious effects at off-target sites. It is regarded as a relatively straightforward and safe approach for a wide range of therapeutic applications. This review discusses the latest advancements and approaches in magnetic cell targeting using endocytosed and surface-bound magnetic nanoparticles as well as in vivo tracking using magnetic resonance imaging (MRI). The most common form of magnetic nanoparticles is superparamagnetic iron oxide nanoparticles (SPION). The biodegradable and biocompatible properties of these magnetically responsive particles and capacity for rapid endocytosis into cells make them a breakthrough in targeted therapy. This review further discusses specific applications of magnetic targeting approaches in cardiovascular tissue engineering including myocardial regeneration, therapeutic angiogenesis, and endothelialization of implantable cardiovascular devices.

12.
Heliyon ; 10(13): e33788, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39040345

RESUMO

The early stage of pancreatic cancer is asymptomatic and the treatment effect is not ideal. The progression to the advanced stage leads to a close relationship between mortality and morbidity. Therefore, there is an urgent need to develop precise and efficient therapeutic strategies to combat pancreatic cancer. In this study, we introduce a near-infrared (NIR) targeted drug delivery nanoparticle for ultrasound (US) imaging to guide magnetothermal/chemotherapy synergistic treatment of pancreatic cancer. Carboxylated polylactic acid (PLGA-PEG-COOH) serves as the structure of the nanoparticles, specifically binding the RGD cyclic peptide for pancreatic cancer targeting activity and promoting tumor aggregation of the nanoparticles. NIR-induced superparamagnetic iron oxide (SPIO) nanoparticles convert near-infrared light into thermal energy, triggering vaporization of perfluoropentane (PFH) droplets to generate PFH bubbles that enhance US imaging and help load doxorubicin (DOX), which are released from nanoparticles. SPIO can also be used for thermal ablation of tumors to improve therapeutic effect in treating pancreatic cancer. The results show that the targeted particles mediated by NIR have the characteristics of targeted drug delivery imaging. The microspheres exhibit strong acoustic and near-infrared responsiveness. Cell proliferation experiments showed that IR-mediated PFH-DOX@PLGA/SPIO-RGD NPs (RNPs) had a higher inhibitory effect on cell proliferation. Animal experiments have shown that RNPS can accumulate highly in the tumor area and show good therapeutic effect. In conclusion, this nanotherapeutic particle is a very promising targeted image-guided photothermal/chemotherapeutic synergistic tumor therapy strategy.

13.
J Proteome Res ; 23(8): 3393-3403, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-38967832

RESUMO

Lysosomes constitute the main degradative compartment of most mammalian cells and are involved in various cellular functions. Most of them are catalyzed by lysosomal proteins, which typically are low abundant, complicating their analysis by mass spectrometry-based proteomics. To increase analytical performance and to enable profiling of lysosomal content, lysosomes are often enriched. Two approaches have gained popularity in recent years, namely, superparamagnetic iron oxide nanoparticles (SPIONs) and immunoprecipitation from cells overexpressing a 3xHA-tagged version of TMEM192 (TMEM-IP). The effect of these approaches on the lysosomal proteome has not been investigated to date. We addressed this topic through a combination of both techniques and proteomic analysis of lysosome-enriched fractions. For SPIONs treatment, we identified altered cellular iron homeostasis and moderate changes of the lysosomal proteome. For overexpression of TMEM192, we observed more pronounced effects in lysosomal protein expression, especially for lysosomal membrane proteins and those involved in protein trafficking. Furthermore, we established a combined strategy based on the sequential enrichment of lysosomes with SPIONs and TMEM-IP. This enabled increased purity of lysosome-enriched fractions and, through TMEM-IP-based lysosome enrichment from SPIONs flow-through and eluate fractions, additional insights into the properties of individual approaches. All data are available via ProteomeXchange with PXD048696.


Assuntos
Lisossomos , Proteômica , Lisossomos/metabolismo , Proteômica/métodos , Humanos , Imunoprecipitação , Nanopartículas Magnéticas de Óxido de Ferro/química , Ferro/metabolismo , Proteoma/análise , Proteoma/metabolismo , Proteínas de Membrana/metabolismo , Células HEK293 , Proteínas
14.
Artigo em Inglês | MEDLINE | ID: mdl-38990437

RESUMO

Superparamagnetic iron oxide nanoparticles (SPIONs) are extensively used as carriers in targeted drug delivery and has several advantages in the field of magnetic hyperthermia, chemodynamic therapy and magnet assisted radionuclide therapy. The characteristics of SPIONs can be tailored to deliver drugs into tumor via "passive targeting" and they can also be coated with tissue-specific agents to enhance tumor uptake via "active targeting". In our earlier studies, we developed HCC specific targeting agent- "phosphorylated galactosylated chitosan"(PGC) for targeting asialoglycoprotein receptors. Considering their encouraging results, in this study we developed a multifunctional targeting system- "phosphorylated galactosylated chitosan-coated magnetic nanoparticles"(PGCMNPs) for targeting HCC. PGCMNPs were synthesized by co-precipitation method and characterized by DLS, XRD, TEM, VSM, elemental analysis and FT-IR spectroscopy. PGCMNPs were evaluated for in vitro antioxidant properties, uptake in HepG2 cells, biodistribution, in vivo toxicity and were also evaluated for anticancer therapeutic potential against NDEA-induced HCC in mice model in terms of tumor status, electrical properties, antioxidant defense status and apoptosis. The characterization studies confirmed successful formation of PGCMNPs with superparamagnetic properties. The internalization studies demonstrated (99-100)% uptake of PGCMNPs in HepG2 cells. These results were also supported by biodistribution studies in which increased iron content (296%) was noted inside the hepatocytes. Further, PGCMNPs exhibited no in vivo toxicity. The anticancer therapeutic potential was evident from observation that PGCMNPs treatment decreased tumor bearing animals (41.6%) and significantly (p ≤ 0.05) lowered tumor multiplicity. Overall, this study indicated that PGCMNPs with improved properties are efficiently taken-up by hepatoma cells and has therapeutic potential against HCC. Further, this agent can be tagged with 32P and hence can offer multimodal cancer treatment options via radiation ablation as well as magnetic hyperthermia.

15.
Front Bioeng Biotechnol ; 12: 1418903, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39007051

RESUMO

Purpose: Osteosarcoma (OS) is the most common type of primary malignant bone tumor. Transducing a functional TP53 gene can effectively inhibit OS cell activity. Poly lactic acid-glycolic acid (PLGA) nanobubbles (NBs) mediated by focused ultrasound (US) can introduce exogenous genes into target cells in animal models, but this technique relies on the passive free diffusion of agents across the body. The inclusion of superparamagnetic iron oxide (SPIO) in microbubbles allows for magnetic-based tissue localization. A low-intensity-focused ultrasound (LIFU) instrument was developed at our institute, and different intensities of LIFU can either disrupt the NBs (RLI-LIFU) or exert cytocidal effects on the target tissues (RHI-LIFU). Based on these data, we performed US-magnetic-mediated TP53-NB destruction and investigated its ability to inhibit OS growth when combined with LIFU both in vitro and in vivo. Methods: Several SPIO/TP53/PLGA (STP) NB variants were prepared and characterized. For the in vitro experiments, HOS and MG63 cells were randomly assigned into five treatment groups. Cell proliferation and the expression of TP53 were detected by CCK8, qRT-PCR and Western blotting, respectively. In vivo, tumor-bearing nude mice were randomly assigned into seven treatment groups. The iron distribution of Perls' Prussian blue-stained tissue sections was determined by optical microscopy. TUNEL-DAPI was performed to examine apoptosis. TP53 expression was detected by qRT-PCR and immunohistochemistry. Results: SPIO/TP53/PLGA NBs with a particle size of approximately 200 nm were prepared successfully. For in vitro experiments, ultrasound-targeted transfection of TP53 overexpression in OS cells and efficient inhibition of OS proliferation have been demonstrated. Furthermore, in a tumor-bearing nude mouse model, RLI-LIFU-magnetic-mediated SPIO/TP53/PLGA NBs increased the transfection efficiency of the TP53 plasmid, resulting in apoptosis. Adding RHI-LIFU to the treatment regimen significantly increased the apoptosis of OS cells in vivo. Conclusion: Combining LIFU and US-magnetic-mediated SPIO/TP53/PLGA NB destruction is potentially a novel noninvasive and targeted therapy for OS.

16.
Int J Nanomedicine ; 19: 7473-7492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39071504

RESUMO

Background: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn. Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord. Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/terapia , Traumatismos da Medula Espinal/fisiopatologia , Nanopartículas Magnéticas de Óxido de Ferro/química , Camundongos , Locomoção/fisiologia , Recuperação de Função Fisiológica/fisiologia , Medula Espinal , Condicionamento Físico Animal , Formação Reticular , Magnetoterapia/métodos , Camundongos Endogâmicos C57BL , Feminino , Potencial Evocado Motor/fisiologia
17.
NanoImpact ; 35: 100515, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38857755

RESUMO

This study explored the response of superoxide dismutase (SOD) under superparamagnetic iron oxide nanoparticles (SPIONs)-induced oxidative stress using combined cellular and molecular methods. Results found that SPIONs induced the inhibition of catalase activity, the U-inverted change of SOD activity and the accumulation of reactive oxygen species (ROS), leading to oxidative damage and cytotoxicity. The change of intracellular SOD activity was resulted from the increase of molecular activity induced by directly interacting with SPIONs and ROS-inhibition of activity. The increase of molecular activity could be attributed to the structural and conformational changes of SOD, which were caused by the direct interaction of SOD with SPIONs. The SOD-SPIONs interaction and its interacting mechanism were explored by multi-spectroscopy, isothermal titration calorimetry and zeta potential assays. SOD binds to SPIONs majorly via hydrophobic forces with the involvement of electrostatic forces. SPIONs approximately adsorb 11 units of SOD molecule with the binding affinity of 2.99 × 106 M-1. The binding sites on SOD were located around Tyr residues, whose hydrophilicity increased upon interacting with SPIONs. The binding to SPIONs loosened the peptide chains, changed the secondary structure and reduced the aggregation state of SOD.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Espécies Reativas de Oxigênio , Superóxido Dismutase , Superóxido Dismutase/metabolismo , Superóxido Dismutase/química , Superóxido Dismutase/genética , Nanopartículas Magnéticas de Óxido de Ferro/química , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo , Animais , Interações Hidrofóbicas e Hidrofílicas , Sítios de Ligação , Ligação Proteica , Catalase/metabolismo , Catalase/química
18.
Polymers (Basel) ; 16(11)2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38891404

RESUMO

The aim of this study is the fabrication of unprecedented neuroelectrodes, replete with exceptional biological and electrical attributes. Commencing with the synthesis of polyethylene glycol and polyethyleneimine-modified iron oxide nanoparticles, the grafting of Dimyristoyl phosphatidylcholine was embarked upon to generate DMPC-SPION nanoparticles. Subsequently, the deposition of DMPC-SPIONs onto a nickel-chromium alloy electrode facilitated the inception of an innovative neuroelectrode-DMPC-SPION. A meticulous characterization of DMPC-SPIONs ensued, encompassing zeta potential, infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction analyses. Evaluations pertaining to hemolysis and cytotoxicity were conducted to ascertain the biocompatibility and biosafety of DMPC-SPIONs. Ultimately, a comprehensive assessment of the biocompatibility, electrochemical properties, and electrophysiological signal acquisition capabilities of DMPC-SPION neuroelectrodes was undertaken. These findings conclusively affirm the exemplary biocompatibility, electrochemical capabilities, and outstanding capability in recording electrical signals of DMPC-SPION neuroelectrodes, with an astounding 91.4% augmentation in electrode charge and a noteworthy 13% decline in impedance, with peak potentials reaching as high as 171 µV and an impressive signal-to-noise ratio of 15.92. Intriguingly, the novel DMPC-SPION neuroelectrodes herald an innovative pathway towards injury repair as well as the diagnosis and treatment of neurological disorders.

19.
Gynecol Oncol ; 187: 145-150, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-38776632

RESUMO

OBJECTIVES: Sentinel lymph node (SLN) detection with superparamagnetic iron oxide (SPIO) nanoparticles has been widely studied and standardized for breast and prostate cancer, but there is scarce evidence concerning its use in vulvar cancer. The objective of this study was to compare SLN detection using a SPIO tracer injected at the time of the surgery detected by a magnetometer, with the standard procedure of using a technetium 99 radioisotope (Tc99) detected by a gamma probe, in patients with vulvar cancer. METHODS: The SPIO vulvar cancer study was a single-center prospective interventional non-inferiority study of SPIO compared to Tc99, conducted between 2016 and 2021 in patients who met the GROINSS-V study inclusion criteria for selective sentinel lymph node dissection in vulvar cancer. RESULTS: We included 18 patients and a total of 41 SLNs. The level of agreement between tracers was 92.7% (80.6%-97.4%), corresponding to 38 out of 41 SLNs, which confirms the non-inferiority of SPIO compared to Tc99. The SLN detection rate per groin was 96.3 (81.7%-99.3) using Tc99 and 100% (87.5%-100%) using SPIO. Both tracers had a detection rate of 100% for positive lymph nodes. CONCLUSIONS: The use of SPIO as a tracer for detecting SLNs in patients with vulvar cancer has shown to be non-inferior to that of the standard radiotracer, with the advantages of not requiring nuclear medicine and being able to inject it at the time of surgery after induction of anesthesia.


Assuntos
Nanopartículas Magnéticas de Óxido de Ferro , Linfonodo Sentinela , Neoplasias Vulvares , Humanos , Feminino , Neoplasias Vulvares/patologia , Neoplasias Vulvares/diagnóstico por imagem , Neoplasias Vulvares/cirurgia , Linfonodo Sentinela/patologia , Linfonodo Sentinela/diagnóstico por imagem , Idoso , Estudos Prospectivos , Pessoa de Meia-Idade , Nanopartículas Magnéticas de Óxido de Ferro/administração & dosagem , Biópsia de Linfonodo Sentinela/métodos , Tecnécio/administração & dosagem , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos/administração & dosagem , Metástase Linfática/diagnóstico por imagem
20.
Natl Sci Rev ; 11(6): nwae100, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38707203

RESUMO

Noise-induced hearing loss (NIHL) is a highly prevalent form of sensorineural hearing damage that has significant negative effects on individuals of all ages and there are no effective drugs approved by the US Food and Drug Administration. In this study, we unveil the potential of superparamagnetic iron oxide nanoparticle assembly (SPIOCA) to reshape the dysbiosis of gut microbiota for treating NIHL. This modulation inhibits intestinal inflammation and oxidative stress responses, protecting the integrity of the intestinal barrier. Consequently, it reduces the transportation of pathogens and inflammatory factors from the bloodstream to the cochlea. Additionally, gut microbiota-modulated SPIOCA-induced metabolic reprogramming in the gut-inner ear axis mainly depends on the regulation of the sphingolipid metabolic pathway, which further contributes to the restoration of hearing function. Our study confirms the role of the microbiota-gut-inner ear axis in NIHL and provides a novel alternative for the treatment of NIHL and other microbiota dysbiosis-related diseases.

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