A.N. Sevchenko Institute of Applied Physical Problems, Belarusian State University, Kurchatova str. 7, Minsk 220045, Belarus.
Research Institute for Physical Chemical Problems, Belarusian State University, Leningradskaya str. 14, Minsk 220006, Belarus.
J Mater Chem B. 2024 Nov 6;12(43):11202-11209. doi: 10.1039/d4tb01663g.
One of the most significant limitations of photodynamic therapy is its reduced efficacy in hypoxic microenvironments, which are typical of the majority of tumors. This work demonstrates that indolenine heptamethine cyanines with different substituents in the polymethine chain and at the terminal heterocycles are effective superoxide generators that can be activated in the near-infrared range. The introduction of an indene moiety into the polymethine chain results in a significant enhancement in photostability compared to dyes with a cyclohexene moiety or an unsubstituted polymethine chain. A hydrophilic indene-bearing heptamethine cyanine dye is shown to be efficiently internalized by Vero E6 cells and to give bright intracellular fluorescence in the 700-850 nm range. Furthermore, the dye generates superoxide anion radicals and induces severe oxidative stress in cells upon activation in the near-infrared range (∼750 nm), ultimately resulting in cell death. The capacity of heptamethine cyanines to generate a superoxide anion radical may prove advantageous for enhancing the efficacy of photodynamic therapy under hypoxic conditions.
光动力疗法的一个最大的局限性是其在缺氧微环境中的疗效降低，而缺氧微环境是大多数肿瘤的典型特征。这项工作表明，具有不同取代基的吲哚啉庚甲川氰染料在聚甲川链和末端杂环上是有效的超氧化物生成剂，可以在近红外范围内被激活。与具有环己烯部分或未取代的聚甲川链的染料相比，将茚部分引入聚甲川链会显著提高光稳定性。实验表明，一种具有亲水性茚部分的庚甲川氰染料可以被 Vero E6 细胞有效内化，并在 700-850nm 范围内产生明亮的细胞内荧光。此外，该染料在近红外区域（约 750nm）被激活时会产生超氧阴离子自由基，并在细胞中诱导严重的氧化应激，最终导致细胞死亡。庚甲川氰染料产生超氧阴离子自由基的能力可能有助于提高缺氧条件下光动力疗法的疗效。
