Ultrasound imaging is clinically established for routine screening examinations of breast, abdomen, neck, and other soft tissues, as well as for therapy monitoring. Microbubbles as vascular contrast agents improve the detection and characterization of cancerous lesions, inflammatory processes, and cardiovascular pathologies. Taking advantage of the excellent sensitivity and specificity of ultrasound for microbubble detection, molecular imaging can be realized by binding antibodies, peptides, and other targeting moieties to microbubble surfaces. Molecular microbubbles directed against various targets such as vascular endothelial growth factor receptor-2, vascular cell adhesion molecule 1, intercellular adhesion molecule 1, selectins, and integrins were developed and were shown in preclinical studies to be able to selectively bind to tumor blood vessels and atherosclerotic plaques. Currently, the first microbubble formulations targeted to angiogenic vessels in prostate cancers are being evaluated clinically. However, microbubbles can be used for more than diagnosis: disintegrating microbubbles emit acoustic forces that are strong enough to induce thrombolysis, and they can also be used for facilitating drug and gene delivery across biologic barriers. This review on the use of microbubbles for ultrasound-based molecular imaging, therapy, and theranostics addresses innovative concepts and identifies areas in which clinical translation is foreseeable in the near future.

Nanomedicines are submicrometer-sized carrier materials designed to improve the biodistribution of i.v. administered (chemo-) therapeutic agents. In recent years, ever more efforts in the nanomedicine field have employed optical imaging (OI) techniques to monitor biodistribution and target site accumulation. Thus far, however, the longitudinal assessment of nanomedicine biodistribution using OI has been impossible, due to limited light penetration (in case of 2D fluorescence reflectance imaging; FRI), and to the inability to accurately allocate fluorescent signals to non-superficial organs (in case of 3D fluorescence molecular tomography; FMT). Using a combination of high-resolution micro-computed tomography (μCT) and FMT, we have here set out to establish a hybrid imaging protocol for non-invasively visualizing and quantifying the accumulation of near-infrared fluorophore-labeled nanomedicines in tissues other than superficial tumors. To this end, HPMA-based polymeric drug carriers were labeled with Dy750, their biodistribution and tumor accumulation were analyzed using FMT, and the resulting data sets were fused with anatomical μCT data sets in which several different physiologically relevant organs were pre-segmented. The robustness of 3D organ segmentation was validated, and the results obtained using 3D CT-FMT were compared to those obtained upon standard 3D FMT and 2D FRI. Our findings convincingly demonstrate that combining anatomical μCT with molecular FMT facilitates the non-invasive assessment of nanomedicine biodistribution. KeywordsNanomedicine; Drug targeting; Biodistribution; FMT; FRI; CT Nanomedicines aim to deliver drugs and imaging agents more efficiently and more specifically to pathological sites. A significant amount of evidence has been obtained over the years exemplifying the superiority of nanomedicine formulations over free drugs, both at the preclinical and at the clinical level. [1][2][3][4][5] Prototypic examples of nanomedicine formulations are liposomes, polymers, micelles and nanoparticles. These submicrometersized carrier materials are designed to modulate the pharmacokinetics and the biodistribution of conjugated or entrapped (chemo-) therapeutic drugs. Upon intravenous (i.v.)

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The endothelial glycocalyx is one of the earliest sites involved during sepsis. This fragile layer is a complex network of cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining the luminal side of endothelial cells with a thickness of about 1 to 3 μm. Sepsis-associated alterations of its structure affect endothelial permeability and result in the liberation of endogenous damage-associated molecular patterns (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating consequences of the proinflammatory cascades in sepsis and septic shock. In this way, the injury to the glycocalyx with the consecutive release of DAMPs contributes to a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the extent of glycocalyx degradation serves as a marker of endothelial dysfunction and sepsis severity. In this review, we highlight the crucial role of the glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis-associated multiple organ failures.

In humans, the ribonuclease A (RNase A) superfamily contains eight different members that have RNase activities, and all of these members are encoded on chromosome 14. The proteins are secreted by a large variety of different tissues and cells; however, a comprehensive understanding of these proteins’ physiological roles is lacking. Different biological effects can be attributed to each protein, including antiviral, antibacterial and antifungal activities as well as cytotoxic effects against host cells and parasites. Different immunomodulatory effects have also been demonstrated. This review summarizes the available data on the human RNase A superfamily and illustrates the significant role of the eight canonical RNases in inflammation and the host defence system against infections.