To investigate the potential of tumor-targeting photoactivated chemotherapy, a chiral ruthenium-based anticancer warhead, Λ/Δ-[Ru(Ph₂phen)₂(OH₂)₂]²⁺, was conjugated to the RGD-containing Ac-MRGDH-NH₂ peptide by direct coordination of the M and H residues to the metal. This design afforded two diastereoisomers of a cyclic metallopeptide, Λ-[1]Cl₂ and Δ-[1]Cl₂. In the dark, the ruthenium-chelating peptide had a triple action. First, it prevented other biomolecules from coordinating with the metal center. Second, its hydrophilicity made [1]Cl₂ amphiphilic so that it self-assembled in culture medium into nanoparticles. Third, it acted as a tumor-targeting motif by strongly binding to the integrin (K_d = 0.061 μM for the binding of Λ-[1]Cl₂ to α_IIbβ₃), which resulted in the receptor-mediated uptake of the conjugate in vitro. Phototoxicity studies in two-dimensional (2D) monolayers of A549, U87MG, and PC-3 human cancer cell lines and U87MG three-dimensional (3D) tumor spheroids showed that the two isomers of [1]Cl₂ were strongly phototoxic, with photoindexes up to 17. Mechanistic studies indicated that such phototoxicity was due to a combination of photodynamic therapy (PDT) and photoactivated chemotherapy (PACT) effects, resulting from both reactive oxygen species generation and peptide photosubstitution. Finally, in vivo studies in a subcutaneous U87MG glioblastoma mice model showed that [1]Cl₂ efficiently accumulated in the tumor 12 h after injection, where green light irradiation generated a stronger tumoricidal effect than a nontargeted analogue ruthenium complex [2]Cl₂. Considering the absence of systemic toxicity for the treated mice, these results demonstrate the high potential of light-sensitive integrin-targeted ruthenium-based anticancer compounds for the treatment of brain cancer in vivo.

Ultraviolet-visible (UV-Vis) spectrometries (absorbance, linear dichroism [LD], and circular dichroism [CD]) are relatively simple techniques that can provide important information on the mode of binding of small molecules (dyes, drugs) to DNA and RNA helices. In this article the spectral characteristics of three families of dyes upon interaction with polynucleotides are reviewed. Each of them is representative for one of the major binding modes: acridines for intercalation, Hoechst dyes for groove binding, and porphyrins for external dye stacking. The purpose is to help the reader who is not accustomed to using these systems to gain a simple picture of what the predominant UV-Vis features of each binding mode are. These data are discussed and tables are provided to collect and compare the absorbance, LD, and CD spectral features of several examples of the three dye families chosen.