Performance of a Nonlinear Magnetic Handheld Probe for Intraoperative Sentinel Lymph Node Detection: A Phantom Study.

OBJECTIVE: This study investigates the performance of the DiffMag handheld probe (nonlinear magnetometry), to be used for sentinel lymph node detection. Furthermore, the performance of DiffMag is compared with a gamma probe and a first-order magnetometer (Sentimag®, linear magnetometry). METHODS: The performance of all three probes was evaluated based on longitudinal distance, transverse distance, and resolving power for two tracer volumes. A phantom was developed to investigate the performance of the probes for a clinically relevant situation in the floor of the mouth (FOM). RESULTS: Considering the longitudinal distance, both DiffMag handheld and Sentimag® probe had comparable performance, while the gamma probe was able to detect at least a factor of 10 deeper. Transverse distances of 13, 11, and 51 mm were measured for the small tracer volume by the DiffMag handheld, Sentimag®, and the gamma probe, respectively. For the large tracer volume this was 21, 18, and 55 mm, respectively. The full width at half maximum, at 7 mm probe height from the phantom surface, was 14, 12, and 18 mm for the small tracer volume and 15, 18, and 25 mm for the large tracer volume with the DiffMag handheld, Sentimag®, and gamma probe, respectively. CONCLUSIONS: With a high resolving power but limited longitudinal distance, the DiffMag handheld probe seems suitable for detecting SLNs which are in close proximity to the primary tumor. In this study, comparable results were shown using linear magnetometry. The gamma probe reached 10 times deeper, but has a lower resolving power compared with the DiffMag handheld probe.

Magnetically Induced Brownian Motion of Iron Oxide Nanocages in Alternating Magnetic Fields and Their Application for Efficient siRNA Delivery.

Hyperthermia of superparamagnetic nanoparticles driven by Néel relaxation in an alternating magnetic field (AMF) has been studied in biomedical areas; however, Brownian motion, induced by another magnetic relaxation mechanism, has not been explored extensively despite its potential in intracellular mechanoresponsive applications. We investigated whether superparamagnetic cage-shaped iron oxide nanoparticles (IO-nanocages), previously demonstrated to carry payloads inside their cavities for drug delivery, can generate Brownian motion by tuning the nanoparticle size at 335 kHz AMF frequency. The motivation of this work is to examine the magnetically driven Brownian motion for the delivery of nanoparticles allowing escape from endosomes before digestion in lysosomes and efficient delivery of siRNA cargoes to the cytoplasm. Superconducting quantum interference device (SQUID) measurements reveal the nanocage size dependence of Brownian relaxation, and a magnetic Brownian motion of 20 nm IO-nanocages improved the efficiency of siRNA delivery while endosomal membranes were observed to be compromised to release IO-nanocages in AMFs during the delivery process.

Atranorin driven by nano materials SPION lead to ferroptosis of gastric cancer stem cells by weakening the mRNA 5-hydroxymethylcytidine modification of the Xc-/GPX4 axis and its expression.

Gastric cancer is a highly malignant tumor. Gastric cancer stem cells (GCSCs) are the main causes of drug resistance, metastasis, recurrence, and poor prognosis. As a secondary metabolite of lichen, Atranorin has a variety of biological effects, such as antibacterial, anti-inflammatory, analgesic, and wound healing; however, its killing effect on GCSCs has not been reported. In this study, we constructed Atranorin complexes comprising superparamagnetic iron oxide nanoparticles (SPION) (Atranorin@SPION). In vitro and in vivo experiments confirmed that Atranorin@SPION could significantly inhibit the proliferation, invasion, angiogenesis, and tumorigenicity of CD44+/ CD24+ GCSCs, and induce oxidative stress injury, Fe2+ accumulation, and ferroptosis. Quantitative real-time reverse transcription PCR and western blotting results showed that Atranorin@SPION not only reduced the expression levels of GCSC stem cell markers and cell proliferation and division markers, but also significantly inhibited the expression levels of key molecules in the cystine/glutamate transporter (Xc-)/glutathione peroxidase 4 (GPX4) and Tet methylcytosine dioxygenase (TET) family proteins. The results of high performance liquid chromatography-mass spectrometry and Dot blotting showed that Atranorin@SPION significantly inhibited the mRNA 5­hydroxymethylcytidine modification of GCSCs. Meanwhile, the results of RNA immunoprecipitation-PCR also indicated that Atranorin@SPIONs significantly reduced the 5-hydroxymethylcytidine modification level of GPX4 and SLC7A11 mRNA 3' untranslated region in GCSCs, resulting in a decrease in their stability, shortening their half-lives and reducing translation activity. Therefore, this study revealed that Atranorin@SPIONs induced ferroptosis of GCSCs by weakening the expression of the Xc-/GPX4 axis and the 5-hydroxymethylcytidine modification of mRNAs in the pathway, thereby achieving their therapeutic effect on gastric cancer.

Preclinical evaluation of a mannose-labeled magnetic tracer for enhanced sentinel lymph node retention in the head and neck.

Sentinel lymph node biopsy in cancers of the head and neck offers demonstrated clinical and diagnostic value, but adoption is limited by concerns about the detrimental consequence to survival of false negative results in a highly curable setting. The aim of this study was to demonstrate potential to overcome this via application of a novel mannose-labeled magnetic iron oxide tracer. In a large animal model, preoperative imaging and intraoperative magnetometer detection were used to identify magnetic lymph nodes. Iron quantification mapped the distribution of tracer within lymphatic levels. Over a 4-week test period, uptake of magnetic tracer in lymph nodes increased in a linear-like fashion, with a substantial percentage of accumulated iron (83%) being retained in the sentinel node. This result indicates a high affinity of mannose-labeled particles to the sentinel node, while providing a means for the magnetometer probe to indicate node status based on intraoperative signal.

EGFR-specific single-chain variable fragment antibody-conjugated Fe3O4/Au nanoparticles as an active MRI contrast agent for NSCLC.

Overexpression of epidermal growth factor receptor (EGFR) is closely associated with a poor prognosis in non-small cell lung cancer (NSCLC), thus making it a promising biomarker for NSCLC diagnosis. Here, we conjugated a single-chain antibody (scFv) targeting EGFR with Fe3O4/Au nanoparticles to form an EGFR-specific molecular MRI bioprobe (scFv@Fe3O4/Au) to better detect EGFR-positive NSCLC tumors in vivo. In vitro, we demonstrated that the EGFR-specific scFv could specifically deliver Fe3O4/Au to EGFR-positive NSCLC cells. In vivo experiments showed that the accumulation of scFv@Fe3O4/Au in tumor tissue was detectable by magnetic resonance imaging (MRI) at the indicated time points after systemic injection. The T2W signal-to-noise ratio (SNR) of EGFR-positive SPC-A1 tumors was significantly decreased after scFv@Fe3O4/Au injection, which was not observed in the tumors of mice injected with BSA@Fe3O4/Au. Furthermore, transmission electron microscopy (TEM) analysis showed the specific localization of scFv@Fe3O4/Au in the SPC-A1 tumor cell cytoplasm. Collectively, the results of our study demonstrated that scFv@Fe3O4/Au might be a useful probe for the noninvasive diagnosis of EGFP-positive NSCLC.

Carboxymethyl dextran-trimethyl chitosan coated superparamagnetic iron oxide nanoparticles: An effective siRNA delivery system for HIV-1 Nef.

Gene therapy, including small interfering RNA (siRNA) technology, is one of the leading strategies that help to improve the outcomes of the current therapeutic systems against HIV-1 infection. The successful therapeutic application of siRNAs requires their safe and efficient delivery to specific cells. Here, we introduce a superparamagnetic iron oxide nanoparticle (SPION) for delivering siRNA against HIV-1 nef (anti-nef siRNA) into two cell lines, HEK293 and macrophage RAW 264.7. SPIONs were coated with trimethyl chitosan (TMC), and thereafter, different concentrations of SPION-TMC were coated with different ratios of a carboxymethyl dextran (CMD) to modify the physicochemical properties and improve the biological properties of the nanocarriers. The nanoparticles exhibited a spherical shape with an average size of 112 nm. The obtained results showed that the designed delivery route enhanced the uptake of siRNA into both HEK293 and RAW 264.7 cells compared with control groups. Moreover, CMD-TMC-SPIONs containing anti-nef siRNA significantly reduced the expression of HIV-1 nef in HEK293 stable cells. The modified siRNA-loaded SPIONs also displayed no toxicity or apoptosis-inducing effects on the cells. The CMD-TMC-SPIONs are suggested as potential nanocarriers for siRNA delivery in gene therapy of HIV-1 infection.

MUC-1 aptamer targeted superparamagnetic iron oxide nanoparticles for magnetic resonance imaging of pancreatic cancer in vivo and in vitro experiment.

This study aims to explore the ability of magnetic resonance imaging (MRI) in mucin 1 (MUC1) modified superparamagnetic iron oxide nanoparticle (SPION) targeting human pancreatic cancer (PC). The MUC1 target-directed probe was prepared through MUC1 conjugated to SPION using the chemical method to assess its physiochemical characteristics, including hydration diameter, surface charge, and magnetic resonance signal. The cytotoxicity of MUC1-USPION was verified by MTS assay. BxPC-3 was cultured with MUC1-USPION and SPION in different concentrations. The combined condition of the targeted probes and cells were observed through Prussian blue staining. The nude mice model of pancreatic cancer was established to investigate the application of the probe. MRI was performed to determine the intensity of the signal of the transplanted tumor, while immunohistochemistry and Western blot analysis were performed to detect the expression of MUC1 after taking the transplanted tumor specimen. The particle size of the prepared molecular probe was 63.5 ± 3.2 nm, and the surface charge was 10.2 mV. Furthermore, the probe solution could significantly reduce the MRI at T2 , and the magnetic resonance transverse relaxation rate (ΔR2 ) has a linear relationship with the concentration of iron in the solution. The cell viability of MUC1-USPION in different concentrations revealed no statistical difference, according to the MTS assay. In vitro, the MRI demonstrated decreased T2WI signal intensity in both groups, especially the targeting group. In vivo, MUC1 could selectively accumulate in the nude mice model, and significantly reduce the T2 signal strength. In subsequent experiments, the expression of MUC1 was high in pancreatic cancer tissues, but low in normal pancreatic tissues, as determined by immunohistochemistry and Western blot analysis. The prepared samples can be combined with pancreatic cancer tissue specificity by in vivo imaging, providing reliable early in vivo imaging data for disease diagnosis.

Superparamagnetic iron oxide nanoparticles as a tool to track mouse neural stem cells in vivo.

Cell transplantation offers a promising approach in many neurological disorders. Neural stem (NS) cells are potential candidates for cell therapy. The ability to track the grafted cells in the host tissue will refine this therapy. Superparamagnetic iron oxide nanoparticles (SPION) have been suggested as a feasible method, but there is no consensus about its safety. Here we investigated the feasibility of label NS cells with SPION and track by MRI after transplantation into mouse striatum with SPION cells and its therapeutic effects by grafting the cells into mouse striatum. We demonstrated that SPION-labeled NS cells display normal patterns of cellular processes including proliferation, migration, differentiation and neurosphere formation. Transmission electron microscopy reveals SPION in the cytoplasm of the cells, which was confirmed by microanalysis. Neurons and astrocytes generated from SPION-labeled NS cells were able to carry nanoparticles after 7 days under differentiation. SPION-labeled NS cells transplanted into striatum of mice were detected by magnetic resonance imaging (MRI) and microscopy 51 days later. In agreement with others reports, we demonstrated that NS cells are able to incorporate SPION in vitro without altering the stemness, and can survive and be tracked by MRI after they have been grafted into mice striatum.

The Impact of Serum Proteins and Surface Chemistry on Magnetic Nanoparticle Colloidal Stability and Cellular Uptake in Breast Cancer Cells.

Superparamagnetic iron oxide nanoparticles (SPIONs) have been extensively studied in biomedical applications for therapeutic or diagnostic purposes. Stability is one of the key determinants dictating successful application of these nanoparticles (NPs) in biological systems. In this study, SPIONs were synthesized and coated with two protective shells-poly(methacrylic acid) (PMAA) or citric acid (CA)-and the stability was evaluated in biologically relevant media together with effect of serum protein supplementation. The stabilities of SPION, SPION-PMAA and SPION-CA in water, DMEM, RPMI, DMEM with 10% (v v-1), and RPMI with 10% (v v-1) fetal bovine serum were determined. Without protective shells, the NPs were not stable and formed large aggregates in all media tested. CA improved the stability of the NPs in water, but was not very effective in improving stability in cell culture media. Addition of serum slightly improved colloidal stability of SPION-CA, whereas inclusion of serum significantly improved the colloidal stability of SPION-PMAA. Serum proteins also found to enhance cellular viability of MCF-7 breast cancer cells after exposure to high concentrations of SPION-PMAA and SPION-CA. Different patterns of serum proteins binding to the NPs were observed, and cellular uptake in MCF-7 cells were investigated. The stabilized SPION-PMAA and SPION-CA NPs showed uptake activity with minimal background attachment. Therefore, the importance of colloidal stability of SPIONs for utilizing in future therapeutic or diagnostic purposes is illustrated.

Very small superparamagnetic iron oxide nanoparticles: Long-term fate and metabolic processing in atherosclerotic mice.

We investigated the biotransformation of very small superparamagnetic iron oxide nanoparticles (VSOP) in atherosclerotic LDLR-/- mice. Transmission electron microscopy revealed an uptake of VSOP not only by macrophages but also by endothelial cells in liver, spleen, and atherosclerotic lesions and their accumulation in the lysosomal compartment. Using magnetic particle spectroscopy (MPS), we show that the majority of VSOP's superparamagnetic iron was degraded within 28 days. MPS spectrum shape indicated changes in the magnetic properties of VSOP during the biodegradation process. Experiments with primary murine bone marrow derived macrophages, primary murine liver sinusoidal endothelial cells, and primary human aortic endothelial cells demonstrated that loading with VSOP induced a differential response of cellular iron homeostasis mechanisms with increased levels of ferritin and iron transport proteins in macrophages and increased levels of ferritin in endothelial cells.

A review of potential applications of MR-guided focused ultrasound for targeting brain tumor therapy.

Magnetic resonance-guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.

Could FA-PG-SPIONs act as a hyperthermia sensitizing agent? An in vitro study.

The therapeutic effect of polyglycerol coated iron oxide nanoparticles (PG-SPIONs, non-targeted nanoparticles) and folic acid-conjugated polyglycerol coated iron oxide nanoparticles (FA-PG-SPIONs, targeted nanoparticles) in combination with hyperthermia on viability of HeLa cells was investigated. It was observed that coated and uncoated SPIONs have spherical shapes with an average diameter of 17.9 ±â€¯2.85 nm and 5.4 ±â€¯0.75 nm, respectively. The penetration rate for cells treated with targeted nanoparticles was shown to be more than that of non-targeted nanoparticles. Moreover, it was revealed that the treatment of cells with ≥ 50 µg/ml FA-PG-SPIONs in combination with hyperthermia induced cytotoxicity in comparison to control cells. The results also showed that increasing the concentrations of targeted nanoparticles (FA-PG-SPIONs) and heating time would increase the value of thermal enhancement factor (TEF). In contrast, TEF values were not increased with increasing heating time and concentrations of non-targeted nanoparticles (PG-SPIONs). On the other hand, TEF values were increased with increasing concentrations and heating time so that the maximum TEF value was obtained at the highest concentration (FA-PG-SPION, 200 µg/ml) as well as the longest heating duration (60 min). Thus, it is concluded that FA-PG-SPIONs with concentrations ≥ 100 µg/ml could be introduced and used as hyperthermia sensitizing agents leading to enhanced cancer therapy efficiency.

Magnetic resonance fingerprinting based on realistic vasculature in mice.

Magnetic resonance fingerprinting (MRF) was recently proposed as a novel strategy for MR data acquisition and analysis. A variant of MRF called vascular MRF (vMRF) followed, that extracted maps of three parameters of physiological importance: cerebral oxygen saturation (SatO2), mean vessel radius and cerebral blood volume (CBV). However, this estimation was based on idealized 2-dimensional simulations of vascular networks using random cylinders and the empirical Bloch equations convolved with a diffusion kernel. Here we focus on studying the vascular MR fingerprint using real mouse angiograms and physiological values as the substrate for the MR simulations. The MR signal is calculated ab initio with a Monte Carlo approximation, by tracking the accumulated phase from a large number of protons diffusing within the angiogram. We first study the identifiability of parameters in simulations, showing that parameters are fully estimable at realistically high signal-to-noise ratios (SNR) when the same angiogram is used for dictionary generation and parameter estimation, but that large biases in the estimates persist when the angiograms are different. Despite these biases, simulations show that differences in parameters remain estimable. We then applied this methodology to data acquired using the GESFIDE sequence with SPIONs injected into 9 young wild type and 9 old atherosclerotic mice. Both the pre injection signal and the ratio of post-to-pre injection signals were modeled, using 5-dimensional dictionaries. The vMRF methodology extracted significant differences in SatO2, mean vessel radius and CBV between the two groups, consistent across brain regions and dictionaries. Further validation work is essential before vMRF can gain wider application.

Quantitative contrast-enhanced MRI with superparamagnetic nanoparticles using ultrashort time-to-echo pulse sequences.

PURPOSE: Conventional MRI using contrast agents is semiquantitative because it is inherently sensitive to extravoxular susceptibility artifacts, field inhomogeneity, partial voluming, perivascular effects, and motion/flow artifacts. Herein we demonstrate a quantitative contrast-enhanced MRI technique using ultrashort time-to-echo pulse sequences for measuring clinically relevant concentrations of ferumoxytol, a superparamagnetic iron oxide nanoparticle contrast agent with high sensitivity and precision in vitro and in vivo. METHODS: The method achieves robust, reproducible results by using rapid signal acquisition at ultrashort time-to-echo (UTE) to produce positive contrast images with pure T1 weighting and little T2* decay. The spoiled gradient echo equation is used to transform UTE intensities directly into concentration using experimentally determined relaxivity constants and image acquisition parameters. RESULTS: A multiparametric optimization of acquisition parameters revealed an optimal zone capable of producing high-fidelity measurements. Clinically relevant intravascular concentrations of ferumoxytol were measured longitudinally in mice with high sensitivity and precision (∼7.1% error). MRI measurements were independently validated by elemental iron analysis of sequential blood draws. Automated segmentation of ferumoxytol concentration yielded high quality three-dimensional images for visualization of perfusion. CONCLUSIONS: This ability to longitudinally quantify blood pool CA concentration is unique to quantitative UTE contrast-enhanced (QUTE-CE) MRI and makes QUTE-CE MRI competitive with nuclear imaging.

Targeted therapy with MXD3 siRNA, anti-CD22 antibody and nanoparticles for precursor B-cell acute lymphoblastic leukaemia.

Conventional chemotherapy for precursor B-cell (preB) acute lymphoblastic leukaemia (ALL) has limitations that could be overcome by targeted therapy. Previously, we discovered a potential therapeutic molecular target, MDX3 (MAX dimerization protein 3), in preB ALL. In this study, we hypothesize that an effective siRNA therapy for preB ALL can be developed using antiCD22 antibody (αCD22 Ab) and nanoparticles. We composed nanocomplexes with super paramagnetic iron oxide nanoparticles (SPIO NPs), αCD22 Abs and MXD3 siRNA molecules based on physical interactions between the molecules. We demonstrated that the MXD3 siRNA-αCD22 Ab-SPIO NP complexes entered leukaemia cells and knocked down MXD3, leading the cells to undergo apoptosis and resulting in decreased live cell counts in the cell line Reh and in primary preB ALL samples in vitro. Furthermore, the cytotoxic effects of the MXD3 siRNA-αCD22 Ab-SPIO NP complexes were significantly enhanced by addition of the chemotherapy drugs vincristine or doxorubicin. We also ruled out potential cytotoxic effects of the MXD3 siRNA-αCD22 Ab-SPIO NP complexes on normal primary haematopoietic cells. Normal B cells were affected while CD34-positive haematopoietic stem cells and non-B cells were not. These data suggest that MXD3 siRNA-αCD22 Ab-SPIO NP complexes have the potential to be a new targeted therapy for preB ALL.

Unveiling the theranostic potential of SPIONs in Alzheimer's disease management.

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.

Controlled assembly of superparamagnetic iron oxide nanoparticle into nanoliposome for Pickering emulsion preparation.

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.

Modified mesoporous silica nanocarriers containing superparamagnetic iron oxide nanoparticle, 5-fluorouracil or oxaliplatin, and metformin as a radiosensitizer, significantly impact colorectal cancer radiation therapy.

This study investigates the anticancer effects of SPION-based silica nanocarriers carrying 5-fluorouracil (5-FU) or oxaliplatin (OX), and metformin (MET) on colorectal cancer cells. Nanocarriers were equipped with pH-responsive gold gatekeepers for controlled release, PEGylation for longer circulation, and folic acid (FA) for targeted delivery. The effects were evaluated by investigating cell viability, cellular uptake, flow cytometry, and clonogenic assay in vitro. The efficacy of the system was also tested in vivo on C57BL/6 mice bearing HT-29 tumors, and potential side effects were evaluated Nanocarriers were synthesized with hydrodynamic diameters of 79.8 nm for 5-FU and 85.2 nm for OX; zeta potentials of -21 and -22 mV, respectively, and remained stable after 72 h. Encapsulation efficiencies were 85 % for 5-FU, 80 % for OX, and 83 % for MET, with loading capacities of 44 %, 38 %, and 41 %, respectively. Drug release in acidic buffer was 38.7 % for 5-FU, 32.8 % for OX, and 43.5 % for MET. MTT assay showed increased toxicity due to FA conjugation, while PEGylation reduced the hemolysis activity. Targeted nanocarriers demonstrated superior cellular uptake and tumor localization compared to non-targeted variants. The combination of 5-FU-MET and OX-MET nanocarriers with radiation therapy (RT) demonstrated the greatest effect on their antitumor activity, accompanied by minimal side effects indicating effective tumor targeting in vivo. MRI and CT imaging further supported these findings. This study underscores the synergistic impact of MET alongside RT on the inhibition of cancer cells and tumor growth for both targeted 5-FU and OX nanocarriers reflecting the significant radiosensitizing properties of MET.

Targeted delivery of elesclomol using a magnetic mesoporous platform improves prostate cancer treatment both in vitro and in vivo.

BACKGROUND: To improve the anticancer properties of elesclomol (ELC), targeted theranostic nanoparticles (NPs; APT-PEG-Au-MMNPs@ELC) were designed to increase the selectivity of the drug delivery system (DDS). MATERIALS AND METHODS: ELC was synthesized and entrapped in the open porous structure of magnetic mesoporous silica nanoparticles (MMNPs). The pore entrance of MMNPs was then blocked using gold gatekeepers. Finally, the external surfaces of the particles were grafted with functional polyethylene glycol (PEG) and EpCAM aptamer to generate biocompatible and targeted NPs. In the next step, the physicochemical properties of prepared NPs were fully evaluated and their anticancer potential was evaluated both in vitro and in vivo. RESULTS: The targeted NPs were successfully synthesized with a final size diameter of 81.13 ± 7.41 nm. The results indicated a pH-dependent release pattern, which sustained for 72 h despite an initial rapid release. Upon exposure to APT-PEG-Au-MMNPs@ELC, higher cytotoxicity was observed in human prostate cancer cells (PC-3) as compared with control Chinese hamster ovary (CHO) cells, indicating higher specificity of targeted NPs against EpCAM-positive cancerous cells. Moreover, APT-PEG-Au-MMNPs@ELC could induce apoptosis in PC-3 cells. In vivo results on a PC-3 xenograft tumor model demonstrated that targeted NPs could significantly inhibit tumor growth and diminish severe side effects of ELC, compared to the free drug. CONCLUSION: Collectively, APT-PEG-Au-MMNPs@ELC could be considered a promising theranostic platform for the targeted delivery of ELC to improve its therapeutic effects in prostate cancer.

Bone marrow stem cells with or without superparamagnetic iron oxide nanoparticles as a magnetic targeting tool: Which is better in regeneration of neurolysed facial nerve? An experimental study.

Aim: This study was performed to evaluate neural regenerative capacities of bone marrow stem cells (BMSCs) with or without superparamagnetic iron oxide nanoparticles (SPIONs) as a magnetic targeting tool after neurolysis of the facial nerve (FN) in albino rats. Methods: Thirty-eight male albino rats were selected. Two of them were euthanized for normal FN histology assessment. Thirty-six rats were injected with ethanol in the FN nerve for neurolysis induction and assessed one week post-operatively by eye blinking test. Animals were divided into three groups, each containing twelve rats: Group I (positive control) was injected with Dulbecco Modified Eagle's medium (DMEM-F12), group II was injected with BMSCs in DMEM-F12, and group III was injected with BMSCs in DMEM-F12 with poly l-lysine coated SPIONs (0.5 mmol/mL). Monitoring of SPIONs in the rat's body was carried out by MRI. A circular neodymium magnet N52 (0.57 T, 2 × 5 mm) was placed on each rat in group III just below the right ear at the site of surgery to attract SPIONs labeled BMSCs, left in place for 24 h, and then removed. From each group, six rats were euthanized at the end of the 4th and 8th week of treatment, respectively. The right FN trunks were extracted for routine histological examination using H&E stain. Immunohistochemical examination by anti-S100B was performed to characterize the thickness of the myelin sheath formed by the Schwann cells. Ultra-structural examination was performed to study changes in axons, myelin sheaths, and Schwann cells. Results: Regeneration of nerve fibers, Schwan cells, and myelin sheaths was better in group II than in groups I and III histologically, immunohistochemically, and ultra-structurally. Conclusion: BMSCs alone could ameliorate FN regeneration better than magnetic targeting treatment using BMSCs labeled with SPIONs.