The targeted delivery of anti-cancer drugs and isotopes is one of the most pursued goals in anti-cancer therapy. One of the prime examples of such an application is the intra-arterial injection of microspheres containing cytostatic drugs or radioisotopes during hepatic embolization procedures. Therapy based on the application of microspheres revolves around vascular occlusion, complemented with local therapy in the form of trans-arterial chemoembolization (TACE) or radioembolization (TARE). The broadest implementation of these embolization strategies currently lies within the treatment of untreatable hepatocellular cancer (HCC) and metastatic colorectal cancer. This review aims to describe the state-of-the-art TACE and TARE technologies investigated in the clinical setting for HCC and addresses current trials and new developments. In addition, chemical properties and advancements in microsphere carrier systems are evaluated, and possible improvements in embolization therapy based on the modification of and functionalization with therapeutical loads are explored.

A new practical, catalytic, and highly stereoselective method for directly accessing 1,1-α,α'-linked 2-deoxy trehalose analogues via AuCl₃-catalyzed dehydrative glycosylation using hemiacetal glycosyl donors and acceptors is described. The method relies on the chemoselective Brønsted acid-type activation of tribenzylated 2-deoxy hemiacetals in the presence of other less reactive hemiacetals.

Background: The occurrence of accidental nerve damage during surgery and the increasing application of image guidance during head-and-neck surgery have highlighted the need for molecular targeted nerve-sparing interventions. The implementation of such interventions relies on the availability of nerve-specific tracers. In this paper, we describe the development of a truncated peptide that has an optimized affinity for protein zero (P0), the most abundant protein in myelin. Methods and Materials: Further C- and N-terminal truncation was performed on the lead peptide Cy5-P0_101–125. The resulting nine Cy5-labelled peptides were characterized based on their photophysical properties, P0 affinity, and in vitro staining. These characterizations were combined with evaluation of the crystal structure of P0, which resulted in the selection of the optimized tracer Cy5-P0_112–125. A near-infrared Cy7-functionalized derivative (Cy7-P0_112–125) was used to perform an initial evaluation of fluorescence-guided surgery in a porcine model. Results: Methodological truncation of the 26-amino-acid lead compound Cy5-P0_101–125 resulted in a size reduction of 53.8% for the optimized peptide Cy5-P0_112–125. The peptide design and the 1.5-fold affinity gain obtained after truncation could be linked to interactions observed in the crystal structure of the extracellular portion of P0. The near-infrared analogue Cy7-P0_112–125 supported nerve illumination during fluorescence-guided surgery in the head-and-neck region in a porcine model. Conclusions: Methodological truncation yielded a second-generation P0-specific peptide. Initial surgical evaluation suggests that the peptide can support molecular targeted nerve imaging.

In non-endemic healthy adults, late-arresting whole sporozoite vaccines have demonstrated a high protective efficacy. To further increase the vaccine potency, we explored options to boost immunogenicity by chemically augmenting SPZ with adjuvants. Key features herein lie in the introduction of chemicals that boost the unique immunogenicity of the SPZ without harming their viability and infectivity. We synthesized two positively charged dye-adjuvant complexes (Cy5-CL307 and Cy5-MDP) that accumulate in SPZs through their mitochondrial potential. Following labelling, the stability of the label was tested. We were able to adjuvant on average 90 % of SPZ with either adjuvant, yielding SPZ^CL307 or SPZ^MDP. Both types of adjuvanted SPZ remained viable (84 % vs 71 %, respectively), motile (78.7 % vs 83.6 %, respectively) and as infective as non-adjuvanted control SPZ. Critically, the loading of adjuvants increased the immunogenicity of the SPZ, as evidenced by the enhanced expression of CD80, CD25, IL-6, IL-8, TNF, IL-1β and IL-10 in monocyte-derived macrophages when stimulated with SPZ^CL307, but not SPZ^MDP (p = 0.018, p = 0.043, p = 0.018, p = 0.018, p = 0.028, p = 0.028 and p = 0.018, respectively). These increases in activation by SPZ^CL307 also translated to 18 % increased CD137 expression (p = 0.01) in circumsporozoite-specific memory CD8⁺ T cells and a trend of 1.6-fold increased expression of perforin (p = 0.064). Our findings indicate that SPZ can be adjuvanted without affecting their viability and infectivity. For SPZ^CL307, but not SPZ^MDP, we found evidence of increased immune activation in in vitro setups and enhanced capacity to boost memory T cell responses. Further optimization of the adjuvanting strategy could help optimize vaccine dosing regimens in the future.

Background: Surgically induced nerve damage is a common but debilitating side effect. By developing tracers that specifically target the most abundant protein in peripheral myelin, namely myelin protein zero (P0), we intend to support fluorescence-guided nerve-sparing surgery. To that end, we aimed to develop a dimeric tracer that shows a superior affinity for P0. Methods: Following truncation of homotypic P0 protein-based peptide sequences and fluorescence labeling, the lead compound Cy5-P0_101–125 was selected. Using a bifunctional fluorescent dye, the dimeric Cy5-(P0_101–125)₂ was created. Assessment of the performance of the mono- and bi-labeled compounds was based on (photo)physical evaluation. This was followed by in vitro assessment in P0 expressing Schwannoma cell cultures by means of fluorescence confocal imaging (specificity, location of binding) and flow cytometry (binding affinity; K_D). Results: Dimerization resulted in a 1.5-fold increase in affinity compared to the mono-labeled counterpart (70.3 +/− 10.0 nM vs. 104.9 +/− 16.7 nM; p = 0.003) which resulted in a 4-fold increase in staining efficiency in P0 expressing Schwannoma cells. Presence of two targeting vectors also improves a pharmacokinetics of labeled compounds by lowering serum binding and optical stability by preventing dye stacking. Conclusions: Dimerization of the nerve-targeting peptide P0_101–125 proves a valid strategy to improve P0 targeting.