Cyclic Ruthenium-Peptide Prodrugs Penetrate the Blood-Brain Barrier and Attack Glioblastoma upon Light Activation in Orthotopic Zebrafish Tumor Models.

ABSTRACT: The blood-brain barrier (BBB) presents one of the main obstacles to delivering anticancer drugs in glioblastoma. Herein, we investigated the potential of a series of cyclic ruthenium-peptide conjugates as photoactivated therapy candidates for the treatment of this aggressive tumor. The three compounds studied, Ru-p(HH), Ru-p(MH), and Ru-p(MM) ([Ru(Ph₂phen)₂ (Ac-X₁RGDX₂-NH₂)]Cl₂ with Ph₂phen = 4,7-diphenyl-1,10-phenanthroline and X₁, X₂ = His or Met), include an integrin-targeted pentapeptide coordinated to a ruthenium warhead via two photoactivated ruthenium-X_1,2 bonds. Their photochemistry, activation mechanism, tumor targeting, and antitumor activity w

SUBMITTER: Zhang L 

PROVIDER: S-EPMC11672551 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature