Abstract 1671: Local release of combretastatin A-4 from NIR-light activatable prodrugs overcomes areal and temporal limitations of photodynamic therapy

Abstract

Abstract A unique prodrug strategy for treating localized cancers, in which NIR light-illuminated prodrug effectively ablates tumors through the combined effects of photodynamic therapy (i.e., singlet oxygen [SO]) and locally released anticancer drugs has been proposed. Due to short distance of action (< 0.04 μs) and short lifetime (< 0.02 μm) of SO, direct damage of PDT is both areally and temporally limited. We hypothesized that the locally released anticancer drugs would overcome the areal and temporal limits of SO. Near IR-activatable prodrug of combretastatin A-4 (CA4), Pc-(L-CA4)2, and its pseudo-prodrug, Pc-(NCL-CA4)2, were evaluated in vitro and in vivo. After partial illumination of a 24 well, all the cells in the prodrug-treated well were killed by the released CA4. Limited areal damage was observed in the pseudo-prodrug-treated wells. A time-dependent cell survival study revealed more extensive cell death in the prodrug-treated cells, due to the sustained damage from the released CA4. Cell cycle analysis and microscopic imaging data demonstrated the typical damage patterns of CA4 in the prodrug-treated cells. A time-dependent histological study showed that prodrug-treated tumors lacked mitotic bodies. The prodrug caused broader and more long-lasting tumor size reduction than did the pseudo-prodrug. These data consistently support that the released CA4 overcomes the areal and temporal limits of SO, providing far superior antitumor effects. Citation Format: Pallavi Rajaputra, Moses Bio, Gregory Nkepang, Pritam Thapa, Sukyung Woo, Youngjae You. Local release of combretastatin A-4 from NIR-light activatable prodrugs overcomes areal and temporal limitations of photodynamic therapy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1671.