Biomimetic hypoxia-triggered RNAi nanomedicine for synergistically mediating chemo/radiotherapy of glioblastoma.

Although RNA interference (RNAi) therapy has emerged as a potential tool in cancer therapeutics, the application of RNAi to glioblastoma (GBM) remains a hurdle. Herein, to improve the therapeutic effect of RNAi on GBM, a cancer cell membrane (CCM)-disguised hypoxia-triggered RNAi nanomedicine was developed for short interfering RNA (siRNA) delivery to sensitize cells to chemotherapy and radiotherapy. Our synthesized CCM-disguised RNAi nanomedicine showed prolonged blood circulation, high BBB transcytosis and specific accumulation in GBM sites via homotypic recognition. Disruption and effective anti-GBM agents were triggered in the hypoxic region, leading to efficient tumor suppression by using phosphoglycerate kinase 1 (PGK1) silencing to enhance paclitaxel-induced chemotherapy and sensitize hypoxic GBM cells to ionizing radiation. In summary, a biomimetic intelligent RNAi nanomedicine has been developed for siRNA delivery to synergistically mediate a combined chemo/radiotherapy that presents immune-free and hypoxia-triggered properties with high survival rates for orthotopic GBM treatment.

Self-Assembly Iron Oxide Nanoclusters for Photothermal-Mediated Synergistic Chemo/Chemodynamic Therapy.

METHODS: Superparamagnetic iron oxide nanoclusters (SPIOCs) were located within the core, which resulted in high photothermal conversion and outstanding generation of reactive oxygen species (ROS). The shell consisted of a human serum albumin- (HSA-) paclitaxel (PTX) layer, which extended the blood circulation time and ensured the effectiveness of the chemotherapy. Arg-Gly-Asp peptides (RGD) were linked to the naked cysteine moieties in HSA to promote the specific targeting of human glioma U87 cells by α v ß 3 integrins. Continuous near-infrared light irradiation triggered and promoted the synergistic chemo/CDT therapy through the photothermal effect. RESULTS: Our SPIOCs@HSA-RGD nanoplatform showed well biocompatibility and could target glioma specifically. Photothermal conversion and ROS burst were detected after continuous 808 nm light irradiation, and a significant antitumor effect was achieved. CONCLUSION: Experimental in vitro and in vivo evaluations showed that our photothermal-mediated chemo/CDT therapy could efficiently inhibit tumor growth and is therefore promising for cancer therapy.

Hypoxia-activated ROS burst liposomes boosted by local mild hyperthermia for photo/chemodynamic therapy.

Single reactive oxygen species (ROS)-mediated therapy, photodynamic therapy (PDT) or chemodynamic therapy (CDT) is severely hindered in hypoxic solid tumor. Herein, to address the urgent challenge, a hypoxia-activated ROS burst liposome has been fabricated to achieve synergistic PDT/CDT that is initiated by the structural dissociation of poly(metronidazole) liposome in hypoxic tumor microenvironment (TME). The therapeutic enhancement of our ROS-blasting treatment is simultaneously regulated by external light-initiated PDT and endogenous iron oxide nanoclusters-triggered CDT, which is synergistically boosted and amplified by localized mild hyperthermia under 808/660 nm coirradiation. More importantly, in vitro and in vivo experiments demonstrate that electron-affinic poly(aminoimidazole) product from hypoxia-responsive transition of poly(metronidazole) polymers could efficiently enhance hypoxic cell apoptosis and induce solid tumor ablation. Thus, this work offers a potential hypoxia-activated ROS burst-PDT/CDT strategy with a superior antitumor efficacy, highlighting a promising clinical application.

Receptor-Mediated Delivery of Astaxanthin-Loaded Nanoparticles to Neurons: An Enhanced Potential for Subarachnoid Hemorrhage Treatment.

Astaxanthin (ATX) is a carotenoid that exerts strong anti-oxidant and anti-inflammatory property deriving from its highly unsaturated molecular structures. However, the low stability and solubility of ATX results in poor bioavailability, which markedly hampers its application as therapeutic agent in clinic advancement. This study investigated a promising way of transferrin conjugated to poly (ethylene glycol) (PEG)-encapsulated ATX nanoparticles (ATX-NPs) on targeted delivery and evaluated the possible mechanism underlying neuroprotection capability. As a result, the ATX integrated into nanocarrier presented both well water-dispersible and biocompatible, primely conquering its limitations. More than that, the transferrin-containing ATX-NPs exhibited enhanced cellular uptake efficiency than that of ATX-NPs without transferrin conjugated in primary cortical neurons. Additionally, compared to free ATX, transferrin-containing ATX-NPs with lower ATX concentration showed powerful neuroprotective effects on OxyHb-induced neuronal damage. Taken together, the improved bioavailability and enhanced neuroprotective effects enabled ATX-NPs as favorable candidates for targeted delivery and absorption of ATX. We believe that these in vitro findings will provide insights for advancement of subarachnoid hemorrhage therapy.

Near-infrared light-activated red-emitting upconverting nanoplatform for T1-weighted magnetic resonance imaging and photodynamic therapy.

Photodynamic therapy (PDT) has increasingly become an efficient and attractive cancer treatment modality based on reactive oxygen species (ROS) that can induce tumor death after irradiation with ultraviolet or visible light. Herein, to overcome the limited tissue penetration in traditional PDT, a novel near-infrared (NIR) light-activated NaScF4: 40% Yb, 2% Er@CaF2 upconversion nanoparticle (rUCNP) is successfully designed and synthesized. Chlorin e6, a photosensitizer and a chelating agent for Mn2+, is loaded into human serum albumin (HSA) that further conjugates onto rUCNPs. To increase the ability to target glioma tumor, an acyclic Arg-Gly-Asp peptide (cRGDyK) is linked to rUCNPs@HSA(Ce6-Mn). This nanoplatform enables efficient adsorption and conversion of NIR light (980 nm) into bright red emission (660 nm), which can trigger the photosensitizer Ce6-Mn complex for PDT and T1-weighted magnetic resonance imaging (T1-weighted MRI) for glioma diagnosis. Our in vitro and in vivo experiments demonstrate that NIR light-activated and glioma tumor-targeted PDT can generate large amounts of intracellular ROS that induce U87 cell apoptosis and suppress glioma tumor growth owing to the deep tissue penetration of irradiated light and excellent tumor-targeting ability. Thus, this nanoplatform holds potential for applications in T1-weighted MRI diagnosis and PDT of glioma for antitumor therapy. STATEMENT OF SIGNIFICANCE: A near-infrared (NIR) light-activated nanoplatform for photodynamic therapy (PDT) was designed and synthesized. The Red-to-Green (R/G) ratio of NaScF4: 40% Yb, 2% Er almost reached 9, a value that was much higher than that of a traditional Yb/Er-codoped upconversion nanoparticle (rUCNP). By depositing a CaF2 shell, the red-emission intensities of the rUCNPs were seven times strong as that of NaScF4: 40% Yb, 2% Er. The enhanced red-emitting rUCNPs could be applied in many fields such as bioimaging, controlled release, and real-time diagnosis. The nanoplatform had a strong active glioma-targeting ability, and all results achieved on subcutaneous glioma demonstrated that our NIR light-activated red-emitting upconverting nanoplatform was efficient for PDT. By loading Ce6-Mn complex into rUCNPs@HSA-RGD, the nanoplatform could be used as a T1-weighted magnetic resonance imaging agent for tumor diagnosis.

pH-Responsive Magnetic Mesoporous Silica-Based Nanoplatform for Synergistic Photodynamic Therapy/Chemotherapy.

By overcoming drug resistance and subsequently enhancing the treatment, the combination therapy of photodynamic therapy (PDT) and chemotherapy has promising potential for cancer treatment. However, the major challenge is how to establish an advanced nanoplatform that can be efficiently guided to tumor sites and can then stably release both chemotherapy drugs and a photosensitizer simultaneously and precisely. In this study, which considered the possibility and targeting efficiency of a magnetic targeting strategy, a novel Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was successfully built; this platform could be employed as an efficient synergistic antitumor nanoplatform with magnetic guidance for highly specific targeting and retention. Doxorubicin (DOX) molecules were loaded into mesoporous silica with high loading capability, and the mesoporous channels were blocked by a polydopamine coating. Human serum albumin (HSA) was conjugated to the outer surface to increase the biocompatibility and blood circulation time, as well as to provide a vehicle for loading photosensitizer chlorin e6 (Ce6). The sustained release of DOX under acidic conditions and the PDT induced by red light exerted a synergistic inhibitory effect on glioma cells. Our experiments demonstrated that the pH-responsive Fe3O4@mSiO2(DOX)@HSA(Ce6) nanoplatform was guided to the tumor region by magnetic targeting and that the nanoplatform suppressed glioma tumor growth efficiently, implying that the system is a highly promising photodynamic therapy/chemotherapy combination nanoplatform with synergistic effects for cancer treatment.

Preoperative evaluation of cochlear implantation through the round window membrane in the facial recess using high-resolution computed tomography.

PURPOSE: We evaluated the risk of cochlear implantation through the round window membrane in the facial recess through a preoperative analysis of the angle between the facial nerve-round window and the cranial midline using high-resolution temporal bone CT. METHODS: Temporal bone CT films of 176 patients with profound sensorineural hearing loss at our hospital from 2013 to 2015 were reviewed. The preoperative temporal bone CT scans of the patients were retrospectively analysed. The vertical distance (d value) from the leading edge of the facial nerve to the posterior wall of the external auditory canal and the angle (α value) between the line from the leading edge of the facial nerve to the midpoint of the round window membrane and the median sagittal line on the round window membrane plane were measured. Based on intraoperative observation, the round window membrane was divided into complete round window membrane exposure (group A), partial exposure (group B), and unexposed (group C) groups, and statistical analysis was performed. RESULTS: The α value could be effectively measured for all 176 patients (62.60 ± 7.12), and the d value could be effectively measured for 95 cases (5.53 ± 1.00). An analysis of the correlation between the α and d values of these 95 cases found a negative correlation. Of the 176 cases, one-way analysis of variance (ANOVA) showed that the differences among the groups were significant [P = 0.000 (< 0.05)]. CONCLUSION: The angle (α value) between the line connecting the leading edge of the facial nerve to the midpoint of the round window and the median sagittal line measured in preoperative CT scans was associated with the difficulty of intraoperatively exposing the round window membrane. When the α value was larger than a certain degree, the difficulty of exposing the round window membrane was increased. In such cases, the surgeon should fully expose the round window membrane during surgery, which could result decrease the likelihood of complications.

Effect of a novel segmentation algorithm on radiologists' diagnosis of breast masses using ultrasound imaging.

We investigated the effect of using a novel segmentation algorithm on radiologists' sensitivity and specificity for discriminating malignant masses from benign masses using ultrasound. Five-hundred ten conventional ultrasound images were processed by a novel segmentation algorithm. Five radiologists were invited to analyze the original and computerized images independently. Performances of radiologists with or without computer aid were evaluated by receiver operating characteristic (ROC) curve analysis. The masses became more obvious after being processed by the segmentation algorithm. Without using the algorithm, the areas under the ROC curve (Az) of the five radiologists ranged from 0.70∼0.84. Using the algorithm, the Az increased significantly (range, 0.79∼0.88; p < 0.001). The proposed segmentation algorithm could improve the radiologists' diagnosis performance by reducing the image speckles and extracting the mass margin characteristics.

[Research on gene expression data based on clustering/classification technology].

As the work of sequencing the genome of the human and many model organisms has been partially or fully finished, the "postgenomic era" has begun. Scientists are turning their focus toward identifying gene function from sequencing. Clustering technology, as one of the important tools of analyzing gene expression data and identifying gene function, has been used widely. In this paper we discuss main clustering technology about gene expression data at present, analyze their advantages and disadvantages, present the methods to solve the problems and give new approaches to study gene expression data.