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Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain malignancy for which there is no cure. The blood-brain barrier is a significant hurdle in the delivery of therapies to GBM. Reported here is an image-guided, iron oxide-based therapeutic delivery nano platform capable of bypassing this physiological barrier by virtue of size and accumulating in the tumor region, delivering its payload. This 25 nm nano platform consists of crosslinked dextran-coated iron oxide nanoparticles labeled with Cy5.5 fluorescent dye and containing antisense oligonucleotide as a payload. The magnetic iron oxide core enables tracking of the nanoparticles through in vivo magnetic resonance imaging, while Cy5.5 dye allows tracking by optical imaging. This report details the monitoring of the accumulation of this nanoparticle platform (termed MN-anti-miR10b) in orthotopically implanted glioblastoma tumors following intravenous injection. In addition, it provides insight into the in vivo delivery of RNA oligonucleotides, a problem that has hampered the translation of RNA therapeutics into the clinic.

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-100β 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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Osteoarthritis is a bone and joint condition characterized pathologically by articular cartilage degenerative damage and can develop into a devastating and permanently disabling disorder. This investigation aimed to formulate the anti-inflammatory drug lornoxicam (LOR) into bile salt-enriched vesicles loaded in an in situ forming hydrogel as a potential local treatment of osteoarthritis. This was achieved by formulating LOR-loaded bilosomes that are also loaded with superparamagnetic iron oxide nanoparticles (SPIONs) for intra-muscular (IM) administration to improve joint targeting and localization by applying an external magnet to the joint. A 3 1 .2 2 full factorial design was employed to develop the bilosomal dispersions and the optimized formula including SPION (LSB) was loaded into a thermosensitive hydrogel. Moreover, in vivo evaluation revealed that the IM administration of LSB combined with the application of an external magnet to the joint reversed carrageen-induced suppression in motor activity and osteoprotegerin by significantly reducing the elevations in mitogen-activated protein kinases, extracellular signal-regulated kinase, and receptor activator of nuclear factor kappa beta/osteoprotegerin expressions. In addition, the histopathological evaluation of knee joint tissues showed a remarkable improvement in the injured joint tissues. The results proved that the developed LSB could be a promising IM drug delivery system for osteoarthritis management., (© 2023. The Author(s).)

This study intends to assess whether iron oxide nanoparticles affect periodontal injury and collagenase-1 (COL-1), and alkaline phosphatase (ALP) in rats. In this study, the ALP activity and Col-1 concentration in rats with periodontal injury were determined.We detected the periodontal histopathological changes and expression of periodontal pocket depth (PD) and attachment loss (AL) by Hematoxylin and eosin (HE) staining.We also detected Col-1 and ALP proteins in periodontal tissues by Western blot. Real-time reverse transcription-polymerase chain reaction (RT-PCR) detected Col-1 and ALP mRNA level in periodontal tissues of rats in each group, while ALP activity and Col-1 concentration in gingival crevicular fluid in model group increased compared to sham group ( P < 0.05). After intervention by iron oxide nanoparticles, ALP activity and Col-1 concentration in the gingival crevicular fluid of model rats decreased greatly ( P < 0.05). The gingival atrophy was more serious in model group, and many inflammatory cells infiltrated into the tissue and destroyed the alveolar tissue. Meanwhile, the periodontal tissue from rats in intervention group was greatly improved, and the degree of alveolar bone destruction was also significantly reduced, while the PD and AL periodontal indexes were significantly inhibited ( P < 0.05). The protein and relative expression showed that the protein and mRNA expressions of ALP and Col-1 in periodontal tissue from model group were lower than those in sham group ( P < 0.05). After intervention by iron oxide nanoparticles, the protein and mRNA expressions of ALP and Col-1 in the periodontal tissues in intervention group increased ( P < 0.05). Iron oxide nanoparticles can thus inhibit the expression of ALP and COL-1 in periodontal injury rats, and improve the periodontal injury tissue.

Iron oxide nanoparticles (magnetite) have been widely used in industry and medicine. However, the safety assessment of magnetite has not been fully completed. The present study was conducted to assess effects of magnetite on carcinogenic activity, using a medium-term bioassay protocol. A total of 100 male Fischer 344 rats, 6 weeks old, were randomly divided into 5 groups of 20 animals each, and given a basal diet and drinking water containing 0 or 0.1% of N-bis(2-hydroxypropyl)nitrosamine (DHPN) for 2 weeks. Two weeks later, the rats were intratracheally instilled magnetite 7 times at an interval of 4 weeks, at the doses of 0, 1.0 or 5.0 mg/kg body weight, and sacrificed at the end of the experimental period of 30 weeks. The multiplicities of macroscopic lung nodules and histopathologically diagnosed bronchiolo-alveolar hyperplasia, induced by DHPN, were both significantly decreased by the high dose of magnetite. The expression of minichromosome maintenance (MCM) protein 7 in non-tumoral alveolar epithelial cells, and the number of CD163-positive macrophages in tumor nodules were both significantly reduced by magnetite. It is suggested that magnetite exerts inhibitory effects against DHPN-induced lung tumorigenesis, by the reduction of alveolar epithelial proliferation and the M2 polarization of tumor-associated macrophages., (Copyright © 2021. Published by Elsevier Inc.)

Iron oxide nanoparticles (IONPs) are used for diverse medical approaches, although the potential health risks, for example adverse effects on brain functions, are not fully clarified. Several in vitro studies demonstrated that the different types of brain cells are able to accumulate IONPs and reported a toxic potential for IONPs, at least for microglia. However, little information is available for the in vivo effects of direct application of IONPs into the brain over time. Therefore, we examined the cellular responses and the distribution of iron in the rat brain at different time points after local infusion of IONPs into selected brain areas. Dispersed IONPs or an equivalent amount of low molecular weight iron complex ferric ammonium citrate or vehicle were infused into the medial prefrontal cortex (mPFC), the caudate putamen (CPu), or the dorsal hippocampus (dHip). Rats were sacrificed 1 day, 1 week, or 4 weeks post-infusion and brain sections were histologically examined for treatment effects on astrocytes, microglia, and neurons. Glial scar formation was observed in the mPFC and CPu 1 week post-infusion independent of the substance and probably resulted from the infusion procedure. Compared to vehicle, IONPs did not cause any obvious additional adverse effects and no additional tissue damage, while the infusion of ferric ammonium citrate enhanced neurodegeneration in the mPFC. Results of iron staining indicate that IONPs were mainly accumulated in microglia. Our results demonstrate that local infusions of IONPs in selected brain areas do not cause any additional adverse effects or neurodegeneration compared to vehicle., (© 2021. The Author(s).)

Single-modal magnetic resonance imaging (MRI) contrast agents sometimes cause signal confusion in clinical diagnosis. Utilizing ligands to endow iron oxide nanoparticles (IO NPs) with excellent dual-modal MRI contrast efficiency might be an effective strategy to improve diagnostic accuracy. This work presents the development of a special ligand-assisted one-pot approach for the preparation of super-hydrophilic magnetic NPs with excellent water dispersion, biocompatibility and T 1 - T 2 dual-modal contrast enhancement properties. In addition, the strong binding capacity between the ethylenediamine tetramethylenephosphonic acid (EDTMP) ligand and water molecules induced by the presence of abundant hydrogen bonds significantly improves spin-lattice ( T 1 ) and spin-spin ( T 2 ) imaging of the IO core. After being modified with the EDTMP ligand, the T 2 relaxation rate of the IO core is dramatically increased from 71.78 mM -1 s -1 to 452.38 mM -1 s -1 , and a moderate T 1 relaxation rate (11.61 mM -1 s -1 ) is observed simultaneously, implying that the NPs with an average size of 9.7 nm may be potential candidates as high-efficiency T 1 - T 2 MRI contrast agents. This fundamental technique of using super-hydrophilicity ligands to endow IO NPs with dual-modal contrast properties without size change and damage in the T 2 contrast effect may provide a useful strategy to facilitate the application of magnetic NPs in the field of medical diagnosis.

Although the key factor affecting the biocompatibility of IONPs is the core size, there is a lack of regular investigation concerning the impact of the parameter on the toxicity of these nanomaterials. Therefore, such studies were carried out in this paper. Their purpose was to compare the influence of PEG-coated-magnetite NPs with the core of 5, 10 and 30 nm on six carefully selected cell lines. The proliferation rate, viability, metabolic activity, migration activity, ROS levels and cytoskeleton architecture of cells have been evaluated for specified incubation periods. These were 24 and 72-h long incubations with IONPs administered in two doses: 5 and 25 µg Fe/ml. A decrease in viability was observed after exposure to the tested NPs for all the analyzed cell lines. This effect was not connected with core diameter but depended on the exposure time to the nanomaterials. IONPs increased not only the proliferation rate of macrophages-being phagocytic cells-but also, under certain conditions stimulated tumor cell divisions. Most likely, the increase in proliferation rate of macrophages contributed to the changes in the architecture of their cytoskeleton. The growth in the level of ROS in cells had been induced mainly by the smallest NPs. This effect was observed for HEK293T cells and two cancerous lines: U87MG (at both doses tested) and T98G (only for the higher dose). This requires further study concerning both potential toxicity of such IONPs to the kidneys and assessing their therapeutic potential in the treatment of glioblastoma multiforme., (© 2021. The Author(s).)