No abstract

We present an economical catalytic procedure to convert readily available 1,2‐diaminobenzenes and terminal epoxides into valuable 1,2,3,4‐tetrahydroquinoxalines in a highly enantioselective fashion. This procedure operates through relay zinc and iridium catalysis, and achieves redox‐neutral and stereoconvergent production of valuable chiral heterocycles from racemic starting materials with water as the only side product. The use of commercially available reagents and catalysts and a convenient procedure also make this catalytic method attractive for practical application.

In drug delivery, the development of nanovesicles that combine both synthetic and cellular components provides added biocompatibility and targeting specificity in comparison to conventional synthetic carriers such as liposomes. Produced through the fusion of U937 monocytes’ membranes and synthetic lipids, our nano-cell vesicle technology systems (nCVTs) showed promising results as targeted cancer treatment. However, no investigation has been conducted yet on the immunogenic profile and the uptake mechanisms of nCVTs. Hence, this study was aimed at exploring the potential cytotoxicity and immune cells’ activation by nCVTs, as well as the routes through which cells internalize these biohybrid systems. The endocytic pathways were selectively inhibited to establish if the presence of cellular components in nCVTs affected the internalization route in comparison to both liposomes (made up of synthetic lipids only) and nano-cellular membranes (made up of biological material only). As a result, nCVTs showed an 8-to-40-fold higher cellular internalization than liposomes within the first hour, mainly through receptor-mediated processes (i.e., clathrin- and caveolae-mediated endocytosis), and low immunostimulatory potential (as indicated by the level of IL-1α, IL-6, and TNF-α cytokines) both in vitro and in vivo. These data confirmed that nCVTs preserved surface cues from their parent U937 cells and can be rationally engineered to incorporate ligands that enhance the selective uptake and delivery toward target cells and tissues.

Colorectal cancer (CRC) is a leading cause of death worldwide. Improved preclinical tumor models are needed to make treatment screening clinically relevant and address disease mortality. Advancements in 3D cell culture have enabled a greater recapitulation of the architecture and heterogeneity of the tumor microenvironment (TME). This has enhanced their pathophysiological relevance and enabled more accurate predictions of tumor progression and drug response in patients. An increasing number of 3D CRC spheroid models include cell populations such as cancer-associated fibroblasts (CAFs), endothelial cells (ECs), immune cells, and gut bacteria to better mimic the in vivo regulation of signaling pathways. Furthermore, cell heterogeneity within the 3D spheroid models enables the identification of new therapeutic targets to develop alternative treatments and test TME-target therapies. In this mini review, we present the advances in mimicking tumor heterogeneity in 3D CRC spheroid models by incorporating CAFs, ECs, immune cells, and gut bacteria. We introduce how, in these models, the diverse cells influence chemoresistance and tumor progression of the CRC spheroids. We also highlight important parameters evaluated during drug screening in the CRC heterocellular spheroids.

We present an economical catalytic procedure to convert readily available 1,2‐diaminobenzenes and terminal epoxides into valuable 1,2,3,4‐tetrahydroquinoxalines in a highly enantioselective fashion. This procedure operates through relay zinc and iridium catalysis, and achieves redox‐neutral and stereoconvergent production of valuable chiral heterocycles from racemic starting materials with water as the only side product. The use of commercially available reagents and catalysts and a convenient procedure also make this catalytic method attractive for practical application.