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

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• 作者：Huimin Yin ; Mat Stephenson ; Jordan Gibson ; Eric Sampson ; Ge Shi ; Tariq Sainuddin ; Susan Monro ; Sherri A. McFarland
• 刊名：Inorganic Chemistry
• 出版年：2014
• 出版时间：May 5, 2014
• 年：2014
• 卷：53
• 期：9
• 页码：4548-4559
• 全文大小：503K
• 年卷期：v.53,no.9(May 5, 2014)
• ISSN：1520-510X

文摘

The purpose of the present investigation was to ascertain whether ³IL excited states with microsecond lifetimes are universally potent for photodynamic applications, and if these long-lived states are superior to their ³MLCT counterparts as in vitro PDT agents. A family of blue-green absorbing, Ru(II)-based transition metal complexes derived from the 蟺-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 ³IL 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 渭M (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 ³IL 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 ³MLCT states of much shorter duration (鈮? 渭s) 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 ³IL excited state lifetime. Therefore, metal complexes that utilize highly photosensitizing ³IL excited states, with suitably long lifetimes ( 1 渭s), are well-poised to elicit PDT at wavelengths even where their molar extinction coefficients are very low (<100 M^鈥? cm^鈥?). Herein we demonstrate that such unexpected reactivity gives rise to very effective PDT in the typical therapeutic window (600鈥?50 nm).