In Vivo Synthetic Anticancer Approach by Resourcing Mouse Blood Albumin as a Biocompatible Artificial Metalloenzyme.

Autor: Imai K; Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan., Muguruma K; Biofunctional Synthetic Chemistry Laboratory, Cluster for Pioneering Research, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.; Laboratory for Chemistry and Life Science, Tokyo Institute of Technology, R1-11, 4259 Nagatsuta-cho, Midori-ku, Yokohama, Kanagawa, 226-8503, Japan., Nakamura A; Biofunctional Synthetic Chemistry Laboratory, Cluster for Pioneering Research, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan., Kusakari Y; Biofunctional Synthetic Chemistry Laboratory, Cluster for Pioneering Research, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan., Chang TC; Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan., Pradipta AR; Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan., Tanaka K; Department of Chemical Science and Engineering, School of Materials and Chemical Technology, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo, 152-8552, Japan.; Biofunctional Synthetic Chemistry Laboratory, Cluster for Pioneering Research, RIKEN, 2-1 Hirosawa, Wako, Saitama, 351-0198, Japan.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Oct 21; Vol. 63 (43), pp. e202411225. Date of Electronic Publication: 2024 Aug 30.
DOI: 10.1002/anie.202411225
Abstrakt: Methods for producing drugs directly at the cancer site, particularly using bioorthogonal metal catalysts, are being explored to mitigate the side effects of therapy. Albumin-based artificial metalloenzymes (ArMs) catalyze reactions in living mice while protecting the catalyst in the hydrophobic pocket. Here, we describe the in situ preparation and application of biocompatible tumor-targeting ArMs using circulating albumin, which is abundant in the bloodstream. The ArM was formed using blood albumin through the intravenous injection of ruthenium conjugated with an albumin-binding ligand; the tumor-targeting unit was conjugated to the ArM using its catalytic activity, and the ArM was transported to the cancer site. The delivered ArM catalyzed a second tagging reaction of the proapoptotic peptide on the cancer surface, successfully suppressing cancer proliferation. This approach, which efficiently leveraged the persisting reactivity twice in vivo, holds promise for future in vivo metal-catalyzed drug synthesis utilizing endogenous albumin.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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