Characterization and Efficacy of a Nanomedical Radiopharmaceutical for Cancer Treatment.

Although much progress has been made over the last decades, there is still a significant clinical need for novel therapies to manage cancer. Typical problems are that solid tumors are frequently inaccessible, aggressive, and metastatic. To contribute to solving some of these issues, we have developed a novel radioisotope-labeled 27 nm nanoparticle, 177Lu-SN201, to selectively target solid tumors via the enhanced permeability and retention effect, allowing irradiation intratumorally. We show that 177Lu-SN201 has robust stealth properties in vitro and anti-tumor efficacy in mouse mammary gland and colon carcinoma models. The possible clinical application is also addressed with single photon emission computed tomography imaging, which confirms uptake in the tumor, with an average activity of 19.4% injected dose per gram (ID/g). The properties of 177Lu-SN201 make it a promising new agent for radionuclide therapy with the potential to target several solid tumor types.

Expanding the Toolbox of R-Selective Amine Transaminases by Identification and Characterization of New Members.

Amine transaminases (ATAs) are used to synthesize enantiomerically pure amines, which are building blocks for pharmaceuticals and agrochemicals. R-selective ATAs belong to the fold type IV PLP-dependent enzymes, and different sequence-, structure- and substrate scope-based features have been identified in the past decade. However, our knowledge is still restricted due to the limited number of characterized (R)-ATAs, with additional bias towards fungal origin. We aimed to expand the toolbox of (R)-ATAs and contribute to the understanding of this enzyme subfamily. We identified and characterized four new (R)-ATAs. The ATA from Exophiala sideris contains a motif characteristic for d-ATAs, which was previously believed to be a disqualifying factor for (R)-ATA activity. The crystal structure of the ATA from Shinella is the first from a Gram-negative bacterium. The ATAs from Pseudonocardia acaciae and Tetrasphaera japonica are the first characterized (R)-ATAs with a shortened/missing N-terminal helix. The active-site charges vary significantly between the new and known ATAs, correlating with their diverging substrate scope.