A Manganese-Based Nanodriver Coordinates Tumor Prevention and Suppression through STING Activation in Glioblastoma.

Glioblastoma (GBM), the most prevalent and aggressive primary malignant brain tumor, exhibits profound immunosuppression and demonstrates a low response rate to current immunotherapy strategies. Manganese cations (Mn2+) directly activate the cGAS/STING pathway and induce the unique catalytic synthesis of 2'3'-cGAMP to facilitate type I IFN production, thereby enhancing innate immunity. Here, a telodendrimer and Mn2+-based nanodriver (PLHM) with a small size is developed, which effectively target lymph nodes through the blood circulation and exhibit tumor-preventive effects at low doses of Mn2+ (3.7 mg kg-1). On the other hand, the PLHM nanodriver also exhibits apparent antitumor effects in GBM-bearing mice via inducing in vivo innate immune responses. The combination of PLHM with doxorubicin nanoparticles (PLHM-DOX NPs) results in superior inhibition of tumor growth in GBM-bearing mice due to the synergistic potentiation of STING pathway functionality by Mn2+ and the presence of cytoplasmic DNA. These findings demonstrate that PLHM-DOX NPs effectively stimulate innate immunity, promote dendritic cell maturation, and orchestrate cascaded infiltration of CD8 cytotoxic T lymphocytes within glioblastomas characterized by low immunogenicity. These nanodivers chelated with Mn2+ show promising potential for tumor prevention and antitumor effects on glioblastoma by activating the STING pathway.

Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.

BACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD. METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model. RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables. CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

Prediction of histopathologic grades of myxofibrosarcoma with radiomics based on magnetic resonance imaging.

PURPOSE: To develop a radiomics-based model from preoperative magnetic resonance imaging (MRI) for predicting the histopathological grades of myxofibrosarcoma. METHODS: This retrospective study included 54 patients. The tumors were classified into high-grade and low-grade myxofibrosarcoma. The tumor size, signal intensity heterogeneity, margin, and surrounding tissue were evaluated on MRI. Using the least absolute shrinkage and selection operator (LASSO) algorithms, 1037 radiomics features were obtained from fat-suppressed T2-weighted images (T2WI), and a radiomics signature was established. Using multivariable logistic regression analysis, three models were built to predict the histopathologic grade of myxofibrosarcoma. A radiomics nomogram represents the integrative model. The three models' performance was evaluated using the receiver operating characteristics (ROC) and calibration curves. RESULTS: The high-grade myxofibrosarcoma had greater depth (P = 0.027), more frequent heterogeneous signal intensity at T2WI (P = 0.015), and tail sign (P = 0.014) than the low-grade tumor. The area under curve (AUC) of these conventional MRI features models was 0.648, 0.656, and 0.668, respectively. Seven radiomic features were selected by LASSO to construct the radiomics signature model, with an AUC of 0.791. The AUC of the integrative model based on radiomics signature and conventional MRI features was 0.875. The integrative model's calibration curve and insignificant Hosmer-Lemeshow test statistic (P = 0.606) revealed good calibration. CONCLUSION: An integrative model using radiomics signature and three conventional MRI features can preoperatively predict low- or high-grade myxofibrosarcoma.

Upregulating HIF-1α to Boost the Survival of Neural Stem Cells via Functional Peptides-Complexed MRI-Visible Nanomedicine for Stroke Therapy.

Neural stem cells (NSCs) transplantation has been considered as a promising strategy for the treatment of ischemic stroke. However, the therapeutic prospect is limited by the poor control over the survival, migration, and maturation of transplanted NSCs. Upregulating hypoxia inducible factor (HIF)-1α expression in stem cells can improve the survival and migration of NSCs grafted for stroke therapy. Functional peptide drugs, which could inhibit endogenous HIF-1α ubiquitination, might be used to effectively upregulate the HIF-1α expression in NSCs, thereby to improve the therapeutic effect in ischemia stroke. Herein, a magnetic resonance imaging (MRI)-visible nanomedicine is developed to codeliver functional peptides and superparamagnetic iron oxide (SPIO) nanoparticles into NSCs. This nanomedicine not only promotes the survival and migration ability of NSCs but also allows an in vivo tracking of transplanted NSCs with MRI. The results demonstrate the great potential of the functional peptides-complexed multifunctional nanomedicine in boosting the therapeutic effect of stem cell-based therapy in stroke.

An all-in-one biomimetic iron-small interfering RNA nanoplatform induces ferroptosis for cancer therapy.

Iron-dependent ferroptosis is a promising therapeutic strategy for cancers. However, the sustained overexpression of the antioxidant glutathione (GSH) in cancer cells substantially limits its therapeutic effect. Seeking efficient approaches that can perform high GSH depletion efficiency remains a significant task. Herein, we construct an all-in-one nanoplatform with functions of tumor targeting, monitoring and treatment for cancer ferroptosis therapy by constructing a homotypic cancer cell membrane-camouflaged iron-small interfering RNA nanohybrid (CM-Fe-siR). The SLC7A11-targeted siRNA in the nanohybrid inhibits the biosynthesis of GSH by cutting off the supply of intracellular cystine, an essential ingredient in GSH synthesis, which subsequently results in the accumulation of reactive oxygen species (ROS) that are generated from Fenton reaction induced by iron. Meanwhile, the intracellular deficiency of GSH inactivates glutathione peroxidase 4 (GPX4, a lipid repair enzyme), which further increases the accretion of lipid peroxides to enhance iron-induced ferroptosis. This biomimetic nanohybrid shows a remarkable anti-cancer effect by triggering sustainable and efficient ferroptosis via these multiple synergistic actions. Besides, the nanohybrids enable in vivo magnetic resonance imaging (MRI) monitoring of therapy. The biomimetic CM-Fe-siR all-in-one nanoplatform may provide an efficient means of ferroptosis therapy for cancers. STATEMENT OF SIGNIFICANCE: Ferroptosis therapy based on the Fenton reaction of iron nanomaterials has aroused much attention in cancer treatment; however, the therapeutic efficacy is greatly inhibited by the sustained overexpression of the antioxidant GSH in cancer cells. It is of great importance to exploit more reagents or techniques performing high GSH depletion efficiency. Here, we facilely construct an all-in-one cancer cell membrane-camouflaged iron-siRNA nanoplatform, which possesses good biosafety, tumor-targeting, and noninvasive MRI monitoring capabilities. It effectively inhibits the GSH synthesis, and further simultaneously promotes the ROS accumulation and GPX4 inactivation, leading to enhanced cancer ferroptosis. This work highlights that the biomimetic iron-siRNA nanohybrids have a high potential in clinical application for imaging-guided cancer ferroptosis therapy.

Unimolecular Nano-contrast Agent with Ultrahigh Relaxivity and Very Long Retention for Magnetic Resonance Lymphography.

Magnetic resonance (MR) imaging is very important for noninvasive lymphography. However, the present MR contrast agents still cannot supply strong enough tissue contrast and long observation window. To improve the performance of contrast agents, we introduce one-dimensional unimolecular nanoparticles with a confined and compact poly(acrylic acid) core as nanoparticulate chelates of gadolinium ions. Thus, obtained nanoparticulate T1 contrast agents give r1 relaxivity as high as 136.3 mM-1·s-1 under 3.0 T. By injection at the footpad of mice, the contrast agents provide excellent contrast enhancement of lymphatic drainage and they may arrive at popliteal lymph nodes within 30 min and reside for more than 80 h. High performance of the present contrast agent is attributed to the confined and compact core of materials that increase hydration number, intershell water diffusion, and decrease rotational motion.

Differential diagnosis of parotid gland tumours: Application of SWI combined with DWI and DCE-MRI.

BACKGROUND: Parotid tumours (PTs) have a variety of pathological types, and the surgical procedures differ depending on the tumour type. However, accurate diagnosis of PTs from the current preoperative examinations is unsatisfactory. METHODS: This retrospective study was approved by the Ethics Committee of our hospital, and the requirement for informed consent was waived. A total of 73 patients with PTs, including 55 benign and 18 malignant tumours confirmed by surgical pathology, were enrolled. All patients underwent diffusion-weighted imaging (DWI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), susceptibility-weighted imaging (SWI), T2-weighted imaging (T2WI), and T1-weighted imaging (T1WI). The signal uniformity and capsule on T2WI, apparent diffusion coefficient (ADC) derived from DWI, semi-quantitative parameter time-intensity curve (TIC) pattern, and quantitative parameters including transfer constant (Ktrans), extravascular extracellular volume fraction (Ve), wash-out constant (Kep) calculated from DCE-MRI, and intratumoural susceptibility signal (ITSS) obtained from SWI were assessed and compared between benign and malignant PTs. Logistic regression analysis was used to select the predictive parameters for the classification of benign and malignant parotid gland tumours, and receiver operating characteristic (ROC) curve analysis was used to evaluate their diagnostic performance. RESULTS: Malignant PTs tended to exhibit a type C TIC pattern, whereas benign tumours tended to be type A and B (p < 0.001). Benign PTs had less ITSS than malignant tumours (p < 0.001). Multivariate analyses showed that ADC, Ve, and ITSS were predictors of tumour classification. ROC analysis showed that the area under the curve (AUC) of ADC, Ve, ITSS, and ADC combined with Ve were 0.623, 0.615, 0.826, and 0.782, respectively, in differentiating between malignant and benign PTs. When ITSS was added, the AUCs of ADC, Ve, and ADC combined with Ve increased to 0.882, 0.848, and 0.930, respectively. CONCLUSION: SWI offers incremental diagnostic value to DWI and DCE-MRI in the characterisation of parotid gland tumours.

Preoperative prediction of axillary sentinel lymph node burden with multiparametric MRI-based radiomics nomogram in early-stage breast cancer.

OBJECTIVES: To develop and validate a multiparametric MRI-based radiomics nomogram for pretreatment predicting the axillary sentinel lymph node (SLN) burden in early-stage breast cancer. METHODS: A total of 230 women with early-stage invasive breast cancer were retrospectively analyzed. A radiomics signature was constructed based on preoperative multiparametric MRI from the training dataset (n = 126) of center 1, then tested in the validation cohort (n = 42) from center 1 and an external test cohort (n = 62) from center 2. Multivariable logistic regression was applied to develop a radiomics nomogram incorporating radiomics signature and predictive clinical and radiological features. The radiomics nomogram's performance was evaluated by its discrimination, calibration, and clinical use and was compared with MRI-based descriptors of primary breast tumor. RESULTS: The constructed radiomics nomogram incorporating radiomics signature and MRI-determined axillary lymph node (ALN) burden showed a good calibration and outperformed the MRI-determined ALN burden alone for predicting SLN burden (area under the curve [AUC]: 0.82 vs. 0.68 [p < 0.001] in training cohort; 0.81 vs. 0.68 in validation cohort [p = 0.04]; and 0.81 vs. 0.58 [p = 0.001] in test cohort). Compared with the MRI-based breast tumor combined descriptors, the radiomics nomogram achieved a higher AUC in test cohort (0.81 vs. 0.58, p = 0.005) and a comparable AUC in training (0.82 vs. 0.73, p = 0.15) and validation (0.81 vs. 0.65, p = 0.31) cohorts. CONCLUSION: A multiparametric MRI-based radiomics nomogram can be used for preoperative prediction of the SLN burden in early-stage breast cancer. KEY POINTS: • Radiomics nomogram incorporating radiomics signature and MRI-determined ALN burden outperforms the MRI-determined ALN burden alone for predicting SLN burden in early-stage breast cancer. • Radiomics nomogram might have a better predictive ability than the MRI-based breast tumor combined descriptors. • Multiparametric MRI-based radiomics nomogram can be used as a non-invasive tool for preoperative predicting of SLN burden in patients with early-stage breast cancer.

Nanomedicine Directs Neuronal Differentiation of Neural Stem Cells via Silencing Long Noncoding RNA for Stroke Therapy.

Transplantation of neural stem cells (NSCs) is a promising treatment paradigm to replace lost neurons and reconstruct the damaged neural circuit after ischemic stroke. However, most transplanted NSCs often differentiate into astrocytes rather than functional neurons, and the poor neuronal differentiation adversely affects the therapeutic outcome of NSCs and limits their clinical translation for stroke therapy. Herein, a theranostic nanomedicine is developed to codeliver superparamagnetic iron oxide nanoparticles (SPIO) and small interfering RNA/antisense oligonucleotides (siRNA/ASO) against Pnky long noncoding RNA (lncRNA) into NSCs. This nanomedicine not only directs neuronal differentiation of NSCs through silencing the Pnky lncRNA but also allows an in vivo tracking of NSCs with magnetic resonance imaging. The enhanced neuronal differentiation of NSCs significantly improved the structural and functional recovery of the damaged brain after a stroke. The results demonstrate the great potential of the multifunctional nanomedicine targeting lncRNA to enhance stem cell-based therapies for a stroke.

Peptide-Modified Nanoparticles for Tumor Targeting and Molecular Imaging.

Nanoparticles hold great promise in tumor targeting and molecular imaging because they can co-deliver therapeutic drugs and imaging agents to the tumor site with a single entity. Nanoparticles modified with ligands against moieties overexpressed on tumor tissues have gained increasing attention due to their active targeting mechanisms. Peptides are well suited for nanoparticle targeting modifications because they are small, easy to synthesize and typically non-immunogenic. Herein, we review the peptide-modified nanoparticles used for tumor targeting therapy and molecular imaging based on the classification of peptide-targeting ligands. The development of targeting peptides and nanoparticles will also be discussed.

Redox Responsive Metal Organic Framework Nanoparticles Induces Ferroptosis for Cancer Therapy.

Ferroptosis is attracting significant attention due to its effectiveness in tumor treatment. The efficiency to produce toxic lipid peroxides (LPOs) at the tumor site plays a key role in ferroptosis. A hybrid PFP@Fe/Cu-SS metal organic framework (MOF) is synthesized and shown to increase intratumoral LPO content through redox reactions generating ·OH. In addition, glutathione (GSH) depletion through disulfide-thiol exchange leads to the inactivation of glutathione peroxide 4 (GPX4), which results in a further increase in LPO content. This MOF exhibits high inhibitory effect on the growth of xenografted Huh-7 tumors in mice. The coadministration of a ferroptosis inhibitor reduces the antitumor effect of the MOF, leading to a restoration of GPX4 activity and an increase in tumor growth. Moreover, the construction of Cu into mesoporous PFP@Fe/Cu-SS not only allows the MOF to be used as a contrast agent for T1 -weighted magnetic resonance imaging, but also renders its photothermal conversion capacity. Thus, near-infrared irradiation is able to induce photothermal therapy and transform the encapsulated liquid perfluoropentane into microbubbles for ultrasound imaging.

Peritumoral administration of IFNß upregulated mesenchymal stem cells inhibits tumor growth in an orthotopic, immunocompetent rat glioma model.

BACKGROUND: Immunotherapy with IFNß is a promising strategy for treating malignant glioma. However, systemic administration of IFNß is inadequate because of low intratumoral concentration and major adverse effects. This study aimed to determine whether mesenchymal stem cells (MSCs) can be used as cellular vehicles to locally deliver IFNß for glioma therapy by using in vivo MRI tracking. METHODS: A recombinant lentiviral vector encoding IFNß and ferritin heavy chain (FTH) reporter genes was constructed to transduce MSCs. The effectiveness and safety of transduction were assessed. After the IFNß and FTH overexpressed MSCs (IFNß-FTH-MSCs) were transplanted into intracranial orthotopic rat F98 gliomas via peritumoral, intracerebral, intratumoral or intra-arterial injection, MRI was performed to track IFNß-FTH-MSCs and to evaluate their therapeutic effect on glioma in vivo, as validated by histologic analysis, quantitative PCR and ELISA assays. RESULTS: MSCs were efficiently and safely transduced to upregulate their IFNß secretion and FTH expression by the constructed lentivirus. After peritumoral injection, IFNß-FTH-MSCs appeared as hypointense signals on MRI, which gradually diminished but remained visible until 11 days. Compared with other administration routes, only peritumoral injection of IFNß-FTH-MSCs showed a remarkable inhibition on the glioma growth. Nearly 30% of IFNß-FTH-MSCs survived up to 11 days after peritumoral injection, while most of IFNß-FTH-MSCs injected via other routes died within 11 days. IFNß-FTH-MSCs grafted peritumorally secreted IFNß persistently, leading to pronounced Batf3+ dendritic cells and CD8+ T lymphocyte infiltration within the glioma. CONCLUSIONS: MSCs can be used as cellular vehicles of IFNß to treat malignant glioma effectively via peritumoral injection.

I6P7 peptide modified superparamagnetic iron oxide nanoparticles for magnetic resonance imaging detection of low-grade brain gliomas.

Glioma, the most severe primary brain malignancy, has very low survival rates and a high level of recurrence. Nowadays, conventional treatments for these patients are suffering a similar plight owing to the distinctive features of the malignant gliomas, for example chemotherapy is limited by the blood-brain barrier while surgery and radiation therapy are affected by the unclear boundaries of tumor from normal tissue. In the present study, a novel superparamagnetic iron oxide (SPIO) nanoprobe for enhanced T2-weighted magnetic resonance imaging (MRI) was developed. A frequently used MRI probe, SPIO nanoparticles, was coated with a silica outer layer and for the first time was covalently modified with interleukin-6 receptor targeting peptides (I6P7) to promote transportation through the blood-brain barrier and recognition of low-grade gliomas. The efficiency of transcytosis across the blood-brain barrier was examined in vitro using a transwell invasion model and in vivo in nude mice with orthotopic low-grade gliomas. The targeting nanoprobe showed significant MRI enhancement and has potential for use in the diagnosis of low-grade gliomas.

Scalable fabrication of metal-phenolic nanoparticles by coordination-driven flash nanocomplexation for cancer theranostics.

Although various nanomaterials have been developed for cancer theranostics, there remains a key challenge for effective integration of therapeutic drugs and diagnostic agents into a single multicomponent nanoparticle via a simple and scalable approach. Moreover, the bottlenecks of nanoformulation in composition controllability, colloidal stability, drug loading capability and batch-to-batch repeatability currently still hinder the clinical translation of nanomedicine. Herein, we report a coordination-driven flash nanocomplexation (cFNC) process to achieve scalable fabrication of doxorubicin-based metal-phenolic nanoparticles (DITH) with a hyaluronic acid surface layer through efficient control of coordination reaction kinetics in a rapid turbulent mixing. The optimized DITH exhibited a small hydrodynamic diameter (84 nm), narrow size distribution, high drug loading capacity (26.6%), high reproducibility and pH-triggered drug release behaviors. The studies indicated that DITH significantly increased cellular endocytosis mediated by CD44+ receptor targeting and accelerated intracellular drug release owing to the sensitivity of DITH to environmental pH stimuli. Furthermore, guided by T1-weighted magnetic resonance (MR) imaging function endowed by ferric ions, DITH exhibited prolonged blood circulation, enhanced tumor accumulation, improved therapeutic performance and decreased toxic side effects after intravenous injection in a MCF-7 tumor-bearing mice model. These results confirmed that the developed DITH is a promising vehicle for cancer theranostic applications, and our work provided a new strategy to promote the development of translational nanomedicine.

Predictive value of pretreatment MRI texture analysis in patients with primary nasopharyngeal carcinoma.

OBJECTIVES: To determine the predictive value of pretreatment MRI texture analysis for progression-free survival (PFS) in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Ethical approval by the institutional review board was obtained for this retrospective analysis. In 79 patients with primary NPC, texture analysis of the primary tumour was performed on pretreatment T2 and contrast-enhanced T1-weighted images (T2WIs and CE-T1WIs). The Cox proportional hazards model was used to determine the association of texture features, tumour volume and the tumour-node-metastasis (TNM) stage with PFS. Survival curves were plotted using the Kaplan-Meier method. The prognostic performance was evaluated with the receiver operating characteristic (ROC) analyses and C-index. RESULTS: Tumour volume (hazard ratio, 1.054; 95% confidence interval [CI], 1.016-1.093) and CE-T1WI-based uniformity (hazard ratio, 0; 95% CI, 0-0.001) were identified as independent predictors for PFS (p < 0.05). Kaplan-Meier analysis showed that smaller tumour volume (less than the cut-off value, 11.699 cm3) and higher CE-T1WI-based uniformity (greater than the cut-off value, 0.856) were associated with improved PFS (p < 0.05). The combination of CE-T1WI-based uniformity with tumour volume and the overall stage predicted PFS better (area under the curve [AUC], 0.825; Cindex, 0.794) than the tumour volume (AUC, 0.659; C-index, 0.616) or the overall stage (AUC, 0.636; C-index, 0.627) did (p < 0.05). CONCLUSIONS: A texture parameter of pretreatment CE-T1WI-based uniformity improves the prediction of PFS in NPC patients. KEY POINTS: • Higher CE-T1WI-based uniformity and smaller tumour volume are predictive of improved PFS in NPC patients. • The combination of CE-T1WI-based uniformity with tumour volume and the overall stage has a better predictive ability for PFS than the tumour volume or the overall stage alone. • Pretreatment MRI texture analysis has a prognostic value for NPC patients.

Polymeric Vector-Mediated Targeted Delivery of Anti-PAK1 siRNA to Macrophages for Efficient Atherosclerosis Treatment.

Atherogenesis, initially induced by endothelial structure alteration and dysfunction, is the main cause of cardiovascular diseases that jeopardize public health. Unfortunately, an efficient strategy for atherosclerosis treatment is still far from satisfying the clinical requirements. Dyslipidemia and chronic inflammatory responses, especially the overexpression of the pro-atherosclerotic factors monocyte chemotactic protein 1 (MCP-1) and interleukin-6 (IL-6) in plaques, represent the key features that promote the development of atherosclerosis. Here, a CD36 antibody-modified small-interfering RNA (siRNA) nanomedicine based on the mPEG-PAsp-(g-PEI) vector was developed for atherosclerosis therapy. In vitro and in vivo studies demonstrated that the synthesized siRNA nanomedicine targeted macrophages, reduced CD36 expression, and inhibited IL-6 and MCP-1 upregulation, and eventually reduced the formation of foam cells and alleviated the pathological process of atherosclerosis. These results indicate that the targeted delivery of anti-PAK1 siRNA using a CD36 antibody-modified polymeric vector represents a novel and efficient strategy for atherosclerosis treatment.

Monitoring of macrophage recruitment enhanced by Toll-like receptor 4 activation with MR imaging in nerve injury.

INTRODUCTION: Macrophage recruitment is critical for nerve regeneration after an injury. The aim of this study was to investigate whether ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle-based MRI could be used to monitor the enhanced macrophage recruitment by Toll-like receptor 4 (TLR4) activation in nerve injury. METHODS: Rats received intraperitoneal injections of either lipopolysaccharide (LPS) or phosphate buffered saline (PBS) or no injection (controls) after a sciatic nerve crush injury. After intravenous injection of the USPIOs (LPS and PBS groups) or PBS (control group), MRI was performed and correlated with histological findings. RESULTS: LPS group showed more remarkable hypointense signals on T2*-weighted imaging and lower T2 values in the crushed nerves than PBS group. The hypointense signal areas were associated with an enhanced recruitment of iron-loaded macrophages to the injured nerves. DISCUSSION: USPIO-enhanced MRI can be used to monitor the enhanced macrophage recruitment by means of TLR4 signal pathway activation in nerve injury. Muscle Nerve, 2018.

In vivo tracking of the tropism of mesenchymal stem cells to malignant gliomas using reporter gene-based MR imaging.

Mesenchymal stem cells (MSCs) have emerged as a promising cellular vehicle for gene therapy of malignant gliomas due to their property of tumor tropism. However, MSCs may show bidirectional and divergent effects on tumor growth. Therefore, a robust surveillance system with a capacity for noninvasive monitoring of the homing, distribution and fate of stem cells in vivo is highly desired for developing stem cell-based gene therapies for tumors. In this study, we used ferritin gene-based magnetic resonance imaging (MRI) to track the tumor tropism of MSCs in a rat orthotopic xenograft model of malignant glioma. MSCs were transduced with lentiviral vectors expressing ferritin heavy chain (FTH) and enhanced green fluorescent protein (eGFP). Intra-arterial, intravenous and intertumoral injections of these FTH transgenic MSCs (FTH-MSCs) were performed in rats bearing intracranial orthotopic C6 gliomas. The FTH-MSCs were detected as hypointense signals on T2- and T2*-weighted images on a 3.0 T clinical MRI. After intra-arterial injection, 17% of FTH-MSCs migrated toward the tumor and gradually diffused throughout the orthotopic glioma. This dynamic process could be tracked in vivo by MRI up to 10 days of follow-up, as confirmed by histology. Moreover, the tumor tropism of MSCs showed no appreciable impact on the progression of the tumor. These results suggest that FTH reporter gene-based MRI can be used to reliably track the tropism and fate of MSCs after their systemic transplantation in orthotopic gliomas. This real-time in vivo tracking system will facilitate the future development of stem cell-based therapies for malignant gliomas.

Multifunctional Hybrid Liposome as a Theranostic Platform for Magnetic Resonance Imaging Guided Photothermal Therapy.

Photothermal therapy (PTT) is an emerging modality for cancer treatment owing to its localized treatment of tumors and easy combination with other therapeutic approaches. An imaging guided tumor ablation will facilitate the implementation of the treatment to boost efficiency. A type of multifunctional hybrid liposome is synthesized by loading indocyanine green (ICG) into a hybrid liposome based on a mixture of hybrid lipid and 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine-diethylene triamine pentacetate acid-gadopentetate dimeglumine (DMPE-DTPA-Gd). The hybrid liposome exhibited high structure stability and narrow size distribution in aqueous media. According to magnetic resonance imaging (MRI), hybrid liposome after tail vein injection accumulated effectively in subcutaneous CT-26 tumor of mice. Moreover, photothermal therapy is able to ablate tumor effectively under MR imaging guidance. Thus, the MRI visible PTT agent-loaded theranostic nanoplatform is promising for effective cancer treatment.

Assessment of the synergic effect of immunomodulation on nerve repair using multiparametric magnetic resonance imaging.

INTRODUCTION: The immune system plays a pivotal role in nerve injury. The aim of this study was to determine the role of multiparametric magnetic resonance imaging (MRI) in evaluation of the synergic effect of immunomodulation on nerve regeneration in neurotmesis. METHODS: Rats with sciatic nerve neurotmesis and surgical repair underwent serial multiparametric MR examinations over an 8-week period after subepineurial microinjection of lipopolysaccharide (LPS) and subsequent subcutaneous injection of FK506 or subepineurial microinjection of LPS or phosphate-buffered saline (PBS) alone. RESULTS: Nerves treated with immunomodulation showed more prominent regeneration than those treated with LPS or PBS alone and more rapid restoration toward normal T2, fractional anisotropy (FA), and radial diffusivity (RD) values than nerves injected with LPS or PBS. DISCUSSION: Nerves treated with immunomodulation exert synergic beneficial effects on nerve regeneration that can be predicted by T2 measurements and FA and RD values. Muscle Nerve 57: E38-E45, 2018.