The anterior cingulate cortex is involved in intero-exteroceptive integration for spatial image transformation of the self-body.

Spatial image transformation of the self-body is a fundamental function of visual perspective-taking. Recent research underscores the significance of intero-exteroceptive information integration to construct representations of our embodied self. This raises the intriguing hypothesis that interoceptive processing might be involved in the spatial image transformation of the self-body. To test this hypothesis, the present study used functional magnetic resonance imaging to measure brain activity during an arm laterality judgment (ALJ) task. In this task, participants were tasked with discerning whether the outstretched arm of a human figure, viewed from the front or back, was the right or left hand. The reaction times for the ALJ task proved longer when the stimulus presented orientations of 0°, 90°, and 270° relative to the upright orientation, and when the front view was presented rather than the back view. Reflecting the increased reaction time, increased brain activity was manifested in a cluster centered on the dorsal anterior cingulate cortex (ACC), suggesting that the activation reflects the involvement of an embodied simulation in ALJ. Furthermore, this cluster of brain activity exhibited overlap with regions where the difference in activation between the front and back views positively correlated with the participants' interoceptive sensitivity, as assessed through the heartbeat discrimination task, within the pregenual ACC. These results suggest that the ACC plays an important role in integrating intero-exteroceptive cues to spatially transform the image of our self-body.

Fundidesulfovibrio magnetotacticus sp. nov., a sulphate-reducing magnetotactic bacterium, isolated from sediments and freshwater of a pond.

A sulphate-reducing magnetotactic bacterium, designated strain FSS-1T, was isolated from sediments and freshwater of Suwa Pond located in Hidaka, Saitama, Japan. Strain FSS-1T was a motile, Gram-negative and curved rod-shaped bacterium that synthesizes bullet-shaped magnetite (Fe3O4) nanoparticles in each cell. Strain FSS-1T was able to grow in the range of pH 6.5-8.0 (optimum, pH 7.0), 22-34 °C (optimum, 28 °C) and with 0-8.0 g l-1 NaCl (optimum, 0-2.0 g l-1 NaCl). Strain FSS-1T grew well in the presence of 50 µM ferric quinate as an iron source. The major fatty acids were anteiso-C15 : 0, iso-C15 : 0 and anteiso-C17 : 0. The major menaquinone was MK-7 (H2). Strain FSS-1T contained desulfoviridin, cytochrome c 3 and catalase, but did not contain oxidase. Strain FSS-1T used fumarate, lactate, pyruvate, malate, formate/acetate, succinate, tartrate, ethanol, 1-propanol, peptone, soytone and yeast extract as electron donors, while the strain used sulphate, thiosulphate and fumarate as electron acceptors. Fumarate was fermented in the absence of electron acceptors. Analysis of the 16S rRNA gene sequence showed that strain FSS-1T is a member of the genus Fundidesulfovibrio. The gene sequence showed 96.7, 95.0, 92.0, 91.2 and 91.4% similarities to the most closely related members of the genera Fundidesulfovibrio putealis B7-43T, Fundidesulfovibrio butyratiphilus BSYT, Desulfolutivibrio sulfoxidireducens DSM 107105T, Desulfolutivibrio sulfodismutans ThAc01T and Solidesulfovibrio magneticus RS-1T, respectively. The DNA G+C content of strain FSS-1T was 67.5 mol%. The average nucleotide identity value between strain FSS-1T and F. putealis B7-43T was 80.7 %. Therefore, strain FSS-1T represents a novel species within the genus Fundidesulfovibrio, for which the name Fundidesulfovibrio magnetotacticus sp. nov. is proposed (=JCM 32405T=DSM 110007T).

Direct Cardiac Epigenetic Reprogramming through Codelivery of 5'Azacytidine and miR-133a Nanoformulation.

Direct reprogramming of cardiac fibroblasts to induced cardiomyocytes (iCMs) is a promising approach to cardiac regeneration. However, the low yield of reprogrammed cells and the underlying epigenetic barriers limit its potential. Epigenetic control of gene regulation is a primary factor in maintaining cellular identities. For instance, DNA methylation controls cell differentiation in adults, establishing that epigenetic factors are crucial for sustaining altered gene expression patterns with subsequent rounds of cell division. This study attempts to demonstrate that 5'AZA and miR-133a encapsulated in PLGA-PEI nanocarriers induce direct epigenetic reprogramming of cardiac fibroblasts to cardiomyocyte-like cells. The results present a cardiomyocyte-like phenotype following seven days of the co-delivery of 5'AZA and miR-133a nanoformulation into human cardiac fibroblasts. Further evaluation of the global DNA methylation showed a decreased global 5-methylcytosine (5-medCyd) levels in the 5'AZA and 5'AZA/miR-133a treatment group compared to the untreated group and cells with void nanocarriers. These results suggest that the co-delivery of 5'AZA and miR-133a nanoformulation can induce the direct reprogramming of cardiac fibroblasts to cardiomyocyte-like cells in-vitro, in addition to demonstrating the influence of miR-133a and 5'AZA as epigenetic regulators in dictating cell fate.

Biological Synthesis of Bioactive Gold Nanoparticles from Inonotus obliquus for Dual Chemo-Photothermal Effects against Human Brain Cancer Cells.

The possibility for an ecologically friendly and simple production of gold nanoparticles (AuNPs) with Chaga mushroom (Inonotus obliquus) (Ch-AuNPs) is presented in this study. Chaga extract's reducing potential was evaluated at varied concentrations and temperatures. The nanoparticles synthesized were all under 20 nm in size, as measured by TEM, which is a commendable result for a spontaneous synthesis method utilizing a biological source. The Ch-AuNPs showed anti-cancer chemotherapeutic effects on human brain cancer cells which is attributed to the biofunctionalization of the AuNPs with Chaga bioactive components during the synthesis process. Further, the photothermal ablation capability of the as-prepared gold nanoparticles on human brain cancer cells was investigated. It was found that the NIR-laser induced thermal ablation of cancer cells was effective in eliminating over 80% of the cells. This research projects the Ch-AuNPs as promising, dual modal (chemo-photothermal) therapeutic candidates for anti-cancer applications.

Interoceptive accuracy is related to the psychological mechanisms of the burning mouth syndrome: a cross-sectional study.

BACKGROUND: Different perspectives are needed to understand the pathophysiology of burning mouth syndrome (BMS), including physiological and psychological standpoints. The significance of interoception in chronic pain has been suggested. However, few studies have investigated this relationship in BMS. Therefore, we examined the role of interoception in BMS. METHODS: This is a cross-sectional study. BMS patients (N = 64) participated in the study. We used interoceptive accuracy (IAc) based on the heartbeat counting task. Then, participants were divided into high and low IAc groups, and their scores on clinical assessment including pain and psychological evaluation were compared. RESULTS: The Visual Analogue Scale scores indicating pain in low IAc patients, but not high IAc patients, were positively correlated with the Beck Depression Inventory-Second Edition (BDI-II) and the State-Trait Anxiety Inventory-State (STAI-S) Scores. CONCLUSIONS: Interoception might play a role in the pathophysiology of BMS.

GANT61 and curcumin-loaded PLGA nanoparticles for GLI1 and PI3K/Akt-mediated inhibition in breast adenocarcinoma.

Current conventional mono and combination therapeutic strategies often fail to target breast cancer tissue effectively due to tumor heterogeneity comprising cancer stem cells (CSCs) and bulk tumor cells. This is further associated with drug toxicity and resistivity in the long run. A nanomedicine platform incorporating combination anti-cancer treatment might overcome these challenges and generate synergistic anti-cancer effects and also reduce drug toxicity. GANT61 and curcumin were co-delivered via polymeric nanoparticles (NPs) for the first time to elicit enhanced anti-tumor activity against heterogeneous breast cancer cell line MCF-7. We adopted the single-emulsion-solvent evaporation method for the preparation of the therapeutic NPs. The GANT61-curcumin PLGA NPs were characterized for their size, shape and chemical properties, and anti-cancer cell studies were undertaken for the plausible explanation of our hypothesis. The synthesized GANT61-curcumin PLGA NPs had a spherical, smooth surface morphology, and an average size of 347.4 d. nm. The NPs induced cytotoxic effects in breast cancer cells at a mid-minimal dosage followed by cell death via autophagy and apoptosis, reduction in their target protein expression along with compromising the self-renewal property of CSCs as revealed by their in vitro cell studies. The dual-drug NPs thus provide a novel perspective on aiding existing anti-cancer nanomedicine therapies to target a heterogeneous tumor mass effectively.

Nano delivery of natural substances as prospective autophagy modulators in glioblastoma.

Glioblastoma is the most destructive type of malignant brain tumor in humans due to cancer relapse. Latest studies have indicated that cancer cells are more reliant on autophagy for survival than non-cancer cells. Autophagy is entitled as programmed cell death type II and studies imply that it is a comeback of cancer cells to innumerable anti-cancer therapies. To diminish the adverse consequences of chemotherapeutics, numerous herbs of natural origin have been retained in cancer treatments. Additionally, autophagy induction occurs via their tumor suppressive actions that could cause cell senescence and increase apoptosis-independent cell death. However, most of the drugs have poor solubility and thus nano drug delivery systems possess excessive potential to improve the aqueous solubility and bioavailability of encapsulated drugs. There is a pronounced need for more therapies for glioblastoma treatment and hereby, the fundamental mechanisms of natural autophagy modulators in glioblastoma are prudently reviewed in this article.

Detection and Analysis of Targeted Biological Cells by Electrophoretic Coulter Method.

Combining the electrophoresis and conventional Coulter methods, we previously proposed the electrophoretic Coulter method (ECM), enabling simultaneous analysis of the size, number, and zeta potential of individual specimens. We validated the ECM experimentally using standard polystyrene particles and red blood cells (RBCs) from sheep; the latter was the first ECM application to biological particles in biotechnology research. However, specimens are prevented from passing through the ECM module aperture, which prevents accurate determination of the zeta potential of each specimen. This problem is caused by electro-osmotic flow (EOF) due to the high zeta potential at the ECM microchannel surfaces. To significantly improve ECM feasibility for biomedicine, we here propose a method to estimate the zeta potential at the ECM microchannel surfaces separate from the zeta potential of each specimen, by investigating the electric-field dependence of the specimen's experimental electrophoretic velocity. We minimize the zeta potential at the microchannel surfaces by applying an organic-molecule coating, and we suppress the surface zeta potential and its resultant EOF by optimizing the microchannel geometry. We demonstrate that the ECM can distinguish between different biological cells using the differences in zeta potential values and/or sizes. We also demonstrate that the ECM can determine the number of biomolecules attached to individual cells and identify whether the average cell state in an analyzed vial is alive or dead. The high-performance ECM can detect cellular morphology alterations, improve immunologic test sensitivity, and identify cell states (living, dying, and dead); this information is clinically useful for early diagnosis and its follow-up.

Type 1 ribotoxin-curcin conjugated biogenic gold nanoparticles for a multimodal therapeutic approach towards brain cancer.

BACKGROUND: Gliomas have been termed recurrent cancers due to their highly aggressive nature. Their tendency to infiltrate and metastasize has posed significant roadblocks to in attaining fool proof treatment solutions. An initiative to curb such a scenario was successfully demonstrated in vitro, utilizing a multi-conceptual gold nanoparticle based photo-thermal and drug combination therapy. METHODS: Gold nanoparticles (Au NPs) were synthesized with a highly environmentally benign process. The Au NPs were PEGylated and conjugated with folate and transferrin antibody to achieve a dual targeted nano-formulation directed towards gliomas. Curcin, a type 1 ribosome inactivating protein, was attached to the Au NPs as the drug candidate, and its multifarious toxic aspects analyzed in vitro. NIR photo-thermal properties of the Au nano-conjugates were studied to selectively ablate the glioma cancer colonies. RESULTS: Highly cyto-compatible, 10-15nm Au NP conjugates were synthesized with pronounced specificity towards gliomas. Curcin was successfully conjugated to the Au NPs with pH responsive drug release. Prominent toxic aspects of curcin, such as ROS generation, mitochondrial and cytoskeletal destabilization were witnessed. Excellent photo-thermal ablation properties of gold nanoparticles were utilized to completely disrupt the cancer colonies with significant precision. CONCLUSION: The multifunctional nanoconjugate projects its competence in imparting complete arrest of the future proliferation or migration of the cancer mass. GENERAL SIGNIFICANCE: With multifunctionality the essence of nanomedicine in recent years, the present nanoconjugate highlights itself as a viable option for a multimodal treatment option for brain cancers and the like.

Synthesis of an ultradense forest of vertically aligned triple-walled carbon nanotubes of uniform diameter and length using hollow catalytic nanoparticles.

It still remains a crucial challenge to actively control carbon nanotube (CNT) structure such as the alignment, area density, diameter, length, chirality, and number of walls. Here, we synthesize an ultradense forest of CNTs of a uniform internal diameter by the plasma-enhanced chemical vapor deposition (PECVD) method using hollow nanoparticles (HNPs) modified with ligand as a catalyst. The diameters of the HNPs and internal cavities in the HNPs are uniform. A monolayer of densely packed HNPs is self-assembled on a silicon substrate by spin coating. HNPs shrink via the collapse of the internal cavities and phase transition from iron oxide to metallic iron in hydrogen plasma during the PECVD process. Agglomeration of catalytic NPs is avoided on account of the shrinkage of the NPs and ligand attached to the NPs. Diffusion of NPs into the substrate, which would inactivate the growth of CNTs, is also avoided on account of the ligand. As a result, an ultradense forest of triple-walled CNTs of a uniform internal diameter is successfully synthesized. The area density of the grown CNTs is as high as 0.6 × 10(12) cm(-2). Finally, the activity of the catalytic NPs and the NP/carbon interactions during the growth process of CNTs are investigated and discussed. We believe that the present approach may make a great contribution to the development of an innovative synthetic method for CNTs with selective properties.

Quantum dot tailored to single wall carbon nanotubes: a multifunctional hybrid nanoconstruct for cellular imaging and targeted photothermal therapy.

Hybrid nanomaterial based on quantum dots and SWCNTs is used for cellular imaging and photothermal therapy. Furthermore, the ligand conjugated hybrid system (FaQd@CNT) enables selective targeting in cancer cells. The imaging capability of quantum dots and the therapeutic potential of SWCNT are available in a single system with cancer targeting property. Heat generated by the system is found to be high enough to destroy cancer cells.

Changes in Resting-State Brain Activity After Cognitive Behavioral Therapy for Chronic Pain: A Magnetoencephalography Study.

Cognitive behavioral therapy (CBT) is believed to be an effective treatment for chronic pain due to its association with cognitive and emotional factors. Nevertheless, there is a paucity of magnetoencephalography (MEG) investigations elucidating its underlying mechanisms. This study investigated the neurophysiological effects of CBT employing MEG and analytical techniques. We administered resting-state MEG scans to 30 patients with chronic pain and 31 age-matched healthy controls. Patients engaged in a 12-session group CBT program. We conducted pretreatment (T1) and post-treatment (T2) MEG and clinical assessments. MEG data were examined within predefined regions of interest, guided by the authors' and others' prior magnetic resonance imaging studies. Initially, we selected regions displaying significant changes in power spectral density and multiscale entropy between patients at T1 and healthy controls. Then, we examined the changes within these regions after conducting CBT. Furthermore, we applied support vector machine analysis to MEG data to assess the potential for classifying treatment effects. We observed normalization of power in the gamma2 band (61-90 Hz) within the right inferior frontal gyrus (IFG) and multiscale entropy within the right dorsolateral prefrontal cortex (DLPFC) of patients with chronic pain after CBT. Notably, changes in pain intensity before and after CBT positively correlated with the alterations of multiscale entropy. Importantly, responders predicted by the support vector machine classifier had significantly higher treatment improvement rates than nonresponders. These findings underscore the pivotal role of the right IFG and DLPFC in ameliorating pain intensity through CBT. Further accumulation of evidence is essential for future applications. PERSPECTIVE: We conducted MEG scans on 30 patients with chronic pain before and after a CBT program, comparing results with 31 healthy individuals. There were CBT-related changes in the right IFG and DLPFC. These results highlight the importance of specific brain regions in pain reduction through CBT.

Insula-cortico-subcortical networks predict interoceptive awareness and stress resilience.

BACKGROUND: Interoception, the neural sensing of visceral signals, and interoceptive awareness (IA), the conscious perception of interoception, are crucial for life survival functions and mental health. Resilience, the capacity to overcome adversity, has been associated with reduced interoceptive disturbances. Here, we sought evidence for our Insula Modular Active Control (IMAC) model that suggest that the insula, a brain region specialized in the processing of interoceptive information, realizes IA and contributes to resilience and mental health via cortico-subcortical connections. METHODS: 64 healthy participants (32 females; ages 18-34 years) answered questionnaires that assess IA and resilience. Mental health was evaluated with the Beck Depression Inventory II that assesses depressive mood. Participants also underwent a 15 minute resting-state functional resonance imaging session. Pearson correlations and mediation analyses were used to investigate the relationship between IA and resilience and their contributions to depressive mood. We then performed insula seed-based functional connectivity analyzes to identify insula networks involved in IA, resilience and depressive mood. RESULTS: We first demonstrated that resilience mediates the relationship between IA and depressive mood. Second, shared and distinct intra-insula, insula-cortical and insula-subcortical networks were associated with IA, resilience and also predicted the degree of experienced depressive mood. Third, while resilience was associated with stronger insula-precuneus, insula-cerebellum and insula-prefrontal networks, IA was linked with stronger intra-insula, insula-striatum and insula-motor networks. CONCLUSIONS: Our findings help understand the roles of insula-cortico-subcortical networks in IA and resilience. These results also highlight the potential use of insula networks as biomarkers for depression prediction.

Multifunctional carboxymethyl cellulose-based magnetic nanovector as a theragnostic system for folate receptor targeted chemotherapy, imaging, and hyperthermia against cancer.

A multifunctional biocompatible nanovector based on magnetic nanoparticle and carboxymethyl cellulose (CMC) was developed. The nanoparticles have been characterized using TEM, SEM, DLS, FT-IR spectra, VSM, and TGA studies. We found that the synthesized carboxymethyl cellulose magnetic nanoparticles (CMC MNPs) were spherical in shape with an average size of 150 nm having low aggregation and superparamagnetic properties. We found that the folate-tagged CMC MNPs were delivered to cancer cells by a folate-receptor-mediated endocytosis mechanism. 5-FU was encapsulated as a model drug for delivering cytotoxicity, and we could demonstrate the sustained release of 5-FU. It was also observed that the FITC-labeled CMC MNPs could effectively enter cells, and the fate of nanoparticles was tracked with Lysotracker. The CMC MNPs could induce significant cell death when an alternating magnetic field was applied. These results indicate that the multifunctional CMC MNPs possess a high drug loading efficiency and high biocompatibility and with low cell cytotoxicity and can be considered to be promising candidates for CMC-based targeted drug delivery, cellular imaging, and magnetic hyperthermia (MHT).

Pharmaceutically versatile sulfated polysaccharide based bionano platforms.

Sulfated polysaccharides are complex polysaccharide molecules with excellent physico-chemical properties and bioactivities. On the basis of origin, they are classified as plant, animal, microbial and chemically synthesized sulfated polysaccharides. They have been widely applied in the fields of material and biological sciences. Biocompatibility and biodegradability of these molecules facilitate their increased use in the nanoparticle synthesis and tissue engineering applications. This review focuses on the structure, function and applications of important types of natural and chemically derived sulfated polysaccharides in the fields of nanotechnology and biomedical sciences. In the first part, we discuss the classification and role of sulfated polysaccharides in various fields. Later, we elaborate the specific bionano applications of commercially important sulfated polysaccharides in ionic gelation, stabilizing, cross-linking, capping and encapsulation of drugs. Finally, we conclude with the future scope and advanced applications of sulfated polysaccharides in various fields of interdisciplinary science. FROM THE CLINICAL EDITOR: This comprehensive review focuses on the structure, function, and applications of natural and chemically derived sulfated polysaccharides in the fields of nanotechnology and biomedical sciences.

Thermal treatment of water-soluble particles formed by compounds composed of carbon nanobelts and C60 molecules.

It was previously shown that spherical particles are self-assembled by compounds composed of C60-(6,6)CNB-C60, where CNB stands for "carbon nanobelt", by mixing two individual solutions of C60 and (6,6)CNB molecules dissolved in 1,2-dichlorobenzene at room temperature. The particles are monodisperse in water thanks to their high absolute value of the zeta potential in water. In this report, we investigate the effect of thermal treatment of the particles on some changes in the physical properties and structures. We find that the particles become electrically conductive after thermal treatment at 600 °C for 1 h. We suppose that the change in the electrical characteristics might have been caused by the structural change of (6,6)CNBs into opened-up ribbons composed of fused benzene rings, which construct networks supported by C60 molecules in the particles, judging by the change in the absorption and mass spectra of the particles after thermal treatment and analysis of a possible change in the structure of C60-(6,6)CNB-C60 based on quantum chemical calculations employing the PM6 method, with which it is known that nanostructures such as carbon nanotubes (CNTs) and (6,6)CNBs can be correctly estimated.

Insula neuroanatomical networks predict interoceptive awareness.

Interoceptive awareness (IA), the subjective and conscious perception of visceral and physiological signals from the body, has been associated with functions of cortical and subcortical neural systems involved in emotion control, mood and anxiety disorders. We recently hypothesized that IA and its contributions to mental health are realized by a brain interoception network (BIN) linking brain regions that receive ascending interoceptive information from the brainstem, such as the amygdala, insula and anterior cingulate cortex (ACC). However, little evidence exists to support this hypothesis. In order to test this hypothesis, we used a publicly available dataset that contained both anatomical neuroimaging data and an objective measure of IA assessed with a heartbeat detection task. Whole-brain Voxel-Based Morphometry (VBM) was used to investigate the association of IA with gray matter volume (GMV) and the structural covariance network (SCN) of the amygdala, insula and ACC. The relationship between IA and mental health was investigated with questionnaires that assessed depressive symptoms and anxiety. We found a positive correlation between IA and state anxiety, but not with depressive symptoms. In the VBM analysis, only the GMV of the left anterior insula showed a positive association with IA. A similar association was observed between the parcellated GMV of the left dorsal agranular insula, located in the anterior insula, and IA. The SCN linking the right dorsal agranular insula with the left dorsal agranular insula and left hyper-granular insula were positively correlated with IA. No association between GMV or SCN and depressive symptoms or anxiety were observed. These findings revealed a previously unknown association between IA, insula volume and intra-insula SCNs. These results may support development of non-invasive neuroimaging interventions, e.g., neurofeedback, seeking to improve IA and to prevent development of mental health problems, such anxiety disorders.

Effects of Thermal Boundary Resistance on Thermal Management of Gallium-Nitride-Based Semiconductor Devices: A Review.

Wide-bandgap gallium nitride (GaN)-based semiconductors offer significant advantages over traditional Si-based semiconductors in terms of high-power and high-frequency operations. As it has superior properties, such as high operating temperatures, high-frequency operation, high breakdown electric field, and enhanced radiation resistance, GaN is applied in various fields, such as power electronic devices, renewable energy systems, light-emitting diodes, and radio frequency (RF) electronic devices. For example, GaN-based high-electron-mobility transistors (HEMTs) are used widely in various applications, such as 5G cellular networks, satellite communication, and radar systems. When a current flows through the transistor channels during operation, the self-heating effect (SHE) deriving from joule heat generation causes a significant increase in the temperature. Increases in the channel temperature reduce the carrier mobility and cause a shift in the threshold voltage, resulting in significant performance degradation. Moreover, temperature increases cause substantial lifetime reductions. Accordingly, GaN-based HEMTs are operated at a low power, although they have demonstrated high RF output power potential. The SHE is expected to be even more important in future advanced technology designs, such as gate-all-around field-effect transistor (GAAFET) and three-dimensional (3D) IC architectures. Materials with high thermal conductivities, such as silicon carbide (SiC) and diamond, are good candidates as substrates for heat dissipation in GaN-based semiconductors. However, the thermal boundary resistance (TBR) of the GaN/substrate interface is a bottleneck for heat dissipation. This bottleneck should be reduced optimally to enable full employment of the high thermal conductivity of the substrates. Here, we comprehensively review the experimental and simulation studies that report TBRs in GaN-on-SiC and GaN-on-diamond devices. The effects of the growth methods, growth conditions, integration methods, and interlayer structures on the TBR are summarized. This study provides guidelines for decreasing the TBR for thermal management in the design and implementation of GaN-based semiconductor devices.

Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis.

Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.

Synergistic targeting of cancer and associated angiogenesis using triple-targeted dual-drug silica nanoformulations for theragnostics.

The targeting and therapeutic efficacy of dye- and dual-drug-loaded silica nanoparticles, functionalized with triple targeting ligands specific towards cancer and neoangiogenesis simultaneously, are discussed. This synergized, high-precision, multitarget concept culminates in an elevated uptake of nanoparticles by cancer and angiogenic cells with amplified proficiency, thereby imparting superior therapeutic efficacy against breast cancer cells and completely disabling the migration and angiogenic sprouting ability of activated endothelial cells. The exceptional multimodal efficiency achieved by this single therapeutic nanoformulation holds promise for the synergistic targeting and treatment of the yet elusive cancer and its related angiogenesis in a single, lethal shot.