Addressing the Biochemical Foundations of a Glucose-Based "Trojan Horse"-Strategy to Boron Neutron Capture Therapy: From Chemical Synthesis to In Vitro Assessment.

Boron neutron capture therapy (BNCT) for cancer is on the rise worldwide due to recent developments of in-hospital neutron accelerators which are expected to revolutionize patient treatments. There is an urgent need for improved boron delivery agents, and herein we have focused on studying the biochemical foundations upon which a successful GLUT1-targeting strategy to BNCT could be based. By combining synthesis and molecular modeling with affinity and cytotoxicity studies, we unravel the mechanisms behind the considerable potential of appropriately designed glucoconjugates as boron delivery agents for BNCT. In addition to addressing the biochemical premises of the approach in detail, we report on a hit glucoconjugate which displays good cytocompatibility, aqueous solubility, high transporter affinity, and, crucially, an exceptional boron delivery capacity in the in vitro assessment thereby pointing toward the significant potential embedded in this approach.

Investigating the Role of Specific Tear Film Lipids Connected to Dry Eye Syndrome: A Study on O-Acyl-ω-hydroxy Fatty Acids and Diesters.

Dry eye syndrome (DES) is a prevalent disease in which the tear film homeostasis is compromised. One of the main causes of DES is thought to be an alteration in the composition of the outermost layer of the tear film, the tear film lipid layer (TFLL), resulting in an increased evaporation of water from the tear film and subsequent drying of the ocular surface. Recent studies have suggested that the specific TFLL lipids, namely, O-acyl-ω-hydroxy fatty acids (OAHFAs) and diesters (DiEs), may play a role in the development of DES. However, their specific connection to DES has remained largely unknown until now because of the lack of information on their biophysical properties and their role in the TFLL. Herein, we have addressed this issue by studying the biophysical properties and evaporation resistance of a library containing 10 synthetic analogues of TFLL OAHFAs and DiEs. Our results show how the variations of chain length and polar groups affect the phase behavior of these lipids at the tear film surface. In addition, the results revealed that the OAHFAs exhibiting a liquid-expanded to solid phase transition formed films with high evaporation resistance, whereas the DiEs were found to have no evaporation resistance. Altogether, our results shed new light on the role of the OAHFAs and DiEs in the TFLL and their connection to DES, suggesting that OAHFAs are likely a key lipid class in maintaining the TFLL evaporation resistance.