Affiliation:
1. Leiden Institute of Chemistry Leiden University Gorlaeus Laboratories PO Box 9502 2300 RA Leiden The Netherlands
2. Department of Chemistry and Biochemistry Texas State University 601 University Dr. San Marcos TX 78666 USA
3. Leiden Academic Centre for Drug Research Leiden University Gorlaeus Laboratories PO Box 9502 2300 RA Leiden The Netherlands
Abstract
AbstractPhotoactivated chemotherapy (PACT) is a promising cancer treatment modality that kills cancer cells via photochemical uncaging of a cytotoxic drug. Most ruthenium‐based photocages used for PACT are activated with blue or green light, which penetrates sub‐optimally into tumor tissues. Here, we report amide functionalization as a tool to fine‐tune the toxicity and excited states of a terpyridine‐based ruthenium photocage. Due to conjugation of the amide group with the terpyridine π system in the excited state, the absorption of red light (630 nm) increased 8‐fold, and the photosubstitution rate rose 5‐fold. In vitro, red light activation triggered inhibition of tubulin polymerization, which led to apoptotic cell death both in normoxic (21 % O2) and hypoxic (1 % O2) cancer cells. In vivo, red light irradiation of tumor‐bearing mice demonstrated significant tumor volume reduction (45 %) with improved biosafety, thereby demonstrating the clinical potential of this compound.
Funder
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
H2020 European Research Council
Subject
General Chemistry,Catalysis