A Ru(II)‐Based Nanoassembly Exhibiting Theranostic PACT Activity in NIR Region

Abstract

upon irradiation, has attracted much attention in recent years. [2] Photoactivation may provide a spatial and temporal control on drug activity and thus reduce sideeffects significantly. Over the past decades, Pt(IV) complexes which can undergo photo reduction to form active Pt(II) species were developed and showed improved efficacy. [3] To address Pt(II) drug-based problems, Ru(II) complexes with anticancer activity were also explored intensively and extensively. [4] Of them, the Ru(II) complexes with PACT potentials are drawing increasing attention due to their expected higher selectivity against tumors. Unlike their Pt(IV) counterparts, Ru(II)-based PACT agents generally rely on ligand photosubstitution reactions, and the anticancer activity originates from either the resultant Ru(II) aqua complexes or the released photolabile ligands or both. [5] To realize clinical application, the currently developed PACT agents, including Ru(II)-based ones, are still faced with a great challenge, i.e., how to shift their photoactivation wavelengths to the phototherapeutic window of 650-900 nm to achieve deeper tissue penetration. The photoinduced ligand dissociation of Ru(II) complexes generally occurs through a triplet metal-centered ( 3 MC) state, which is thermally accessed from a low-lying triplet metal to ligand charge transfer ( 3 MLCT) state. [5] Further extension of the absorption of a Ru(II) complex often enlarges the energy gap between 3 MC and 3 MLCT states, consequently leads to a quite low quantum yield of ligand photodissociation. By innovative utilization of strained ligands to lower the 3 MC state energy, some elegant works successfully moved the excitation wavelengths to around 600 nm and maintained effective ligand photodissociation. [6] There is still a large room for further optimizing photoactivation to the ideal window. Besides, the examined Ru(II)-based PACT agents are almost non-emissive at room temperature, which limits their theranostic applications.Two-photon excitation is a powerful strategy to realize photoactivation in the near-infrared (NIR) region, [7] however, to the best of our knowledge has not been applied in Ru(II) based PACT agents yet. Due to the small two-photon absorption cross sections (δ 2 ) of common Ru(II) complexes (<300 Goeppert Mayer (GM), 1 GM = 10 −50 cm 4 s photon −1 ), [7] sensitization is Photoactivated chemotherapy (PACT) has appealing merits over traditional chemotherapy as well as photodynamic therapy (PDT) by virtue of its spatial and temporal control on drug activity and oxygen-independent mechanisms of action. However, the short photoactivation wavelengths, e.g., visible light-activated Ru(II)-based PACT agents, limit the clinical application severely. In this work, a facile construction of supramolecular nanoparticles from a poly(ethylene glycol) (PEG)-modified [Ru(dip) 2 (py-SO 3 )] + (abbreviated as Ru-PEG, dip = 4,7-diphenyl-1,10-phenanthroline, py-SO 3 = pyridine-2-sulfonate) and 1,3-phenylenebis(pyren-1-ylmethanone) (BP) is shown. While Ru-PEG may under...

The Development of Ru(II)-Based Photoactivated Chemotherapy Agents

“…Additionally, two-photon absorption has been utilized for photoactivation of Ru(II) complexes, in which the prodrugs are activated by radiation in the PDT window [ 93 , 94 , 95 , 96 ]. Recently, by simply using a pyrene-modified-terpyridine (tpy-Py) as the labile bidentate ligand, Zhou et al designed and synthesized a promising Ru(II) polypyridine complex 44 , which shows dual PACT and PDT activity upon efficient two-photon excitation in the NIR region [ 97 ].…”