In Vitro Multiwavelength PDT with 3IL States: Teaching Old Molecules New Tricks

Citations Over TimeTop 10% of 2014 papers

Abstract

The purpose of the present investigation was to ascertain whether (3)IL excited states with microsecond lifetimes are universally potent for photodynamic applications, and if these long-lived states are superior to their (3)MLCT counterparts as in vitro PDT agents. A family of blue-green absorbing, Ru(II)-based transition metal complexes derived from the π-expansive dppn ligand was prepared and characterized according to its photodynamic activity against HL-60 cells, and toward DNA in cell-free media. Complexes in this series that are characterized by low-energy and long-lived (3)IL excited states photocleaved DNA with blue, green, red, and near-IR light. This panchromatic photodynamic effect translated to in vitro multiwavelength photodynamic therapy (PDT) with red-light cytotoxicities as low as 1.5 μM (EC50) for the parent complex and 400 nM for its more lipophilic counterpart. This potency is similar to that achieved with Ru(II)-based dyads containing long-lived (3)IL excitons located on appended pyrenyl units, and appears to be a general property of sufficiently long-lived excited states. Moreover, the red PDT observed for certain members of this family was almost 5 times more potent than Photofrin with therapeutic indices 30 times greater. Related Ru(II) complexes having lowest-lying (3)MLCT states of much shorter duration (≤1 μs) did not yield DNA photodamage or in vitro PDT with red or near-IR light, nor did the corresponding Os(II) complex with a submicrosecond (3)IL excited state lifetime. Therefore, metal complexes that utilize highly photosensitizing (3)IL excited states, with suitably long lifetimes (≫ 1 μs), are well-poised to elicit PDT at wavelengths even where their molar extinction coefficients are very low (<100 M(-1) cm(-1)). Herein we demonstrate that such unexpected reactivity gives rise to very effective PDT in the typical therapeutic window (600-850 nm).

Related Papers

• → Perfluorocarbon nanoparticles enhance reactive oxygen levels and tumour growth inhibition in photodynamic therapy(2015)923 cited
• → Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions(2017)75 cited
• → Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions(2017)4 cited
• → Research advances in action mechanisms of photodynamic therapy and photosensitizer(2016)
• → Fluorous photosensitizers enhance photodynamic therapy with perfluorocarbon nanoemulsions(2017)