regenerative medicine and remains a major challenge. A multitude of technologies have been described to control the spatial organization of cells in 3D engineered heart constructs including mechanical strain/load [1] and chronic electrical stimulation. [2] Other approaches to guide cellular organization have been reported using microfluidic platforms, [3] light-triggered activation of biomolecules, [4] and 3D bioprinting. [5] However, these techniques often involve elaborate, macroscale stimulation systems and are not always suitable for the fabrication of detailed microarchitectures in vitro as each pattern requires new molds, posts, or frames. [6] The next generation of dynamic systems may be designed to respond to user-defined size and shape triggers for controlling cellular organization on the macroscale without the need for external mechanical supports or material cues. Magnetic procedures to manipulate and remotely control cellular behavior represent a promising approach for fabrication of tissuelike constructs. In particular, magnetic nanoparticles (MNPs) have gained increased attention for use in biomedical applications such as magnetic targeting of stem cells [7] and genes, [8] development of scaffold-free multilayer structures, [9] and spatial patterning of aggregates. [10] Magnetic techniques are advantageous due to their high precision and accuracy. To date, magnetic fabrication of biological structures has been illustrated by the assembly of biomembranes made of organized yeast, [11] the formation of "artificial retinas" by magnetic field modulation of chiromagnetic nanoparticles, [12] or the engineering of vocal folds, [13] among others.Here, we report a new platform for engineering tissue morphologies with controlled geometries. Specifically, we used magnetic fields to direct the assembly and patterning of magnetized human cardiomyocytes (CMs) labeled with MNPs in collagenbased hydrogels. Our system enables dynamic manipulation of cells within 3D biomaterials that can be applied to engineer patterned tissues to investigate cellular and tissue behavior. Furthermore, the simplicity and the faithful reproduction of our approach will enable the creation of customized 3D constructs with a new range of complementary implementations such as in biomedical devices, soft robotics, and flexible electronics.First, we designed functionalized MNPs to target and label human induced pluripotent-stem-cell-derived cardiomyocytes (hiPSC-CMs, Figure 1a). For that purpose, we conjugated an antisignal-regulatory protein alpha (SIRPA) cell surface mono clonal antibody [14] labeled with a fluorophore to three types of MNPsThe ability to manipulate cellular organization within soft materials has important potential in biomedicine and regenerative medicine; however, it often requires complex fabrication procedures. Here, a simple, cost-effective, and one-step approach that enables the control of cell orientation within 3D collagen hydrogels is developed to dynamically create various tailored microstructures of cardiac...

Antibiotic resistance is a serious global health problem necessitating new bactericidal approaches such as nanomedicines. Dendrimersomes (DSs) have recently become a valuable alternative nanocarrier to polymersomes and liposomes due to their molecular definition and synthetic versatility. Despite this, their biomedical application is still in its infancy. Inspired by the localized antimicrobial function of neutrophil phagosomes and the versatility of DSs, a simple three-component DS-based nanoreactor with broad-spectrum bactericidal activity is presented. This was achieved by encapsulation of glucose oxidase (GOX) and myeloperoxidase (MPO) within DSs (GOX-MPO-DSs), self-assembled from an amphiphilic Janus dendrimer, that possesses a semipermeable membrane. By external addition of glucose to GOX-MPO-DS, the production of hypochlorite ( − OCl), a highly potent antimicrobial, by the enzymatic cascade was demonstrated. This cascade nanoreactor yielded a potent bactericidal effect against two important multidrug resistant pathogens, Staphylococcus aureus ( S. aureus ) and Pseudomonas aeruginosa ( P. aeruginosa ), not observed for H 2 O 2 producing nanoreactors, GOX-DS. The production of highly reactive species such as – OCl represents a harsh bactericidal approach that could also be cytotoxic to mammalian cells. This necessitates the development of strategies for activating – OCl production in a localized manner in response to a bacterial stimulus. One option of locally releasing sufficient amounts of substrate using a bacterial trigger (released toxins) was demonstrated with lipidic glucose-loaded giant unilamellar vesicles (GUVs), envisioning, e.g ., implant surface modification with nanoreactors and GUVs for localized production of bactericidal agents in the presence of bacterial growth.

The aim of this study was to assess the efficacy of PRRT in patients with advanced neuroendocrine tumors (NETs). Patients and Methods. From January 2007 to August 2011, we enrolled 65 patients (m/f 38/27; mean age 65 years, range 33–83) with advanced NETs having enhanced SSTR expression, treated with PRRT. The enhanced expression of SSTR was assessed using 68Ga-DOTATOC/DOTATATE PET/CT. Among all the enrolled patients, 6 of them were excluded from the present analysis since they voluntarily interrupted treatment. Mean activity/cycle of 2.6 GBq (90Y-DOTATOC/DOTATATE) or 6.0 GBq (177Lu-DOTATOC/DOTATATE) was administrated intravenously (max 9 cycles). Results. Complete response (CR) was found in 1/59 (2%) patients, partial remission (PR) in 24/59 (40.5%) patients, stable disease (SD) in 24/59 (40.5%), and progression (PD) in 10/59 (17%) patients. The overall tumor response rate (CR + PR) was 42.5%. In 40.5% of patients, the disease could be stabilized. Overall, 49 out of 59 patients had no tumor progression (83%). Twelve patients out of 59 (20%) had grade 2-3 hematological side effects including anemia, thrombocytopenia, and leukopenia. Long-term nephrotoxicity was observed in 3 patients (2 moderate, 1 severe). Conclusions. PRRT is a promising perspective for patients with advanced NETs.

Extracellular vesicles (EVs) are secreted by the vast majority of cells and are being intensively studied due to their emerging involvement in a variety of cellular communication processes. However, the study of their cellular uptake and fate has been hampered by difficulty in imaging EVs against the cellular background. Here, we show that EVs combined with hydrophobic gold nanoclusters (AuNCs) can self-assemble into supraparticles, offering an excellent labeling strategy for high-resolution electron microscopic imaging in vitro. We have tracked and visualized the reuptake of breast cancer cell-derived EV AuNC supraparticles into their parent cells, from early endocytosis to lysosomal degradation, using focused ion beam-scanning electron microscopy (FIB-SEM). The presence of gold within the EVs and lysosomes was confirmed via DF-STEM EDX analysis of lift-out sections. The demonstrated formation of AuNC EV supraparticles will facilitate future applications in EV imaging as well as the EV-assisted cellular delivery of AuNCs.

A tuneable peptide-crosslinked, temperature-sensitive nanogel platform for protein delivery in response to MMP-7, which is overexpressed in many pathologies, is presented.

Molecular imaging of extracellular vesicles in vitro via Raman metabolic labelling.

BackgroundCarcinoids enter the differential diagnosis of the solitary pulmonary nodule. Bronchial carcinoids have been traditionally considered as FDG-PET negative but recent studies have found an higher sensitivity of integrated FDG-PET/CT for the detection of these neoplasms. The purpose of this study was to investigate the value of integrated FDG-PET/CT for the evaluation of SPN suspected to be carcinoids.MethodsAll patients with pathologically proven bronchial carcinoids who had FDG-PET/CT scans between 2006 and 2012 have been retrospectively reviewed. PET/CT was performed with the same scanner and the same technique for all patients. The following data were retrieved: age, sex CT findings (side, location, size, shape, margins), SUVmax, type of operation, pathological findings (size and number of mitoses). Regarding PET findings, only SUVmax was considered, whereas the visual assessment was not undertaken. Carcinoids were defined as typical and atypical and as central and peripheral. The long-term follow-up was also recorded. The SUVmax was compared with the other clinical, radiological and pathological variables to find any significant difference or correlation.ResultsTwenty-five patients were retrieved, 24 typical and one atypical carcinoid, 21 peripheral and 4 central lesions. The mean diameter on CT-scan was 25.3 mm and the clinical size correlated well with the pathological size. Sixty percent of the tumors were ovoid and 68% had smooth margins. The mean SUVmax was 3.6 (range 1.4-12.9). All the lesions were completely resected. The regression analysis showed a direct correlation between the SUVmax and the tumor size (p = 0.004). No further correlations were found between the SUVmax and the other variables. None of the patients had recurrent disease or died during the follow-up.ConclusionsOur study showed that FDG-PET/CT might be a useful tool in the evaluation of SPNs suspected to be bronchial carcinoids. When a solitary pulmonary nodule shows an ovoid/round shape and smooth margins on the CT scan and demonstrates an FDG uptake higher than that of the normal lung and with a SUVmax value >1-1.5, a carcinoid should be suspected. If benign lesions can be presumably excluded, surgical resection or at least a biopsy of the lesion is recommended.

Purpose The prognostic meaning of a post-stress ejection fraction (EF) decrease detected by perfusion gated SPECT is still unclear. We therefore followed up patients with post-stress EF decrease in the absence of stress-induced perfusion abnormalities. Methods We prospectively enrolled 57 consecutive patients with post-stress EF drop ≥5 EF units and summed difference score (SDS)≤1. They were followed up for more than 1 year and their outcome was compared with a group of sex-and agematched controls with the same SDS but without EF decrease. Results During follow-up there were 13 events (1 cardiac death, 1 non-fatal myocardial infarction, 1 congestive heart failure and 10 late revascularizations). In the control group we registered six events. There was a significant difference (p<0.0001) between the event-free survival curves of the two groups. ConclusionThe event rate of patients with post-stress EF decrease≥5 EF units is relatively high and is significantly worse than that of a control group of patients with similarly normal SDS but without EF changes. Therefore, a post-stress EF decrease without stress-induced perfusion abnormalities should be cautiously interpreted.