Abstract 4506: Photocaged molecules in targeted drug delivery.

We have developed a new targeted therapy that uses light to deliver cytotoxic agents into cancer cells. This strategy is based on the concept of photocaging in which a biologically active molecule is made inactive by the attachment of a light-cleavable blocking group. Upon exposure to UV radiation the photocleavable entity is removed and the biologically active molecule is released. Using this concept we have designed a prodrug that consists of a cell impermeable hydrophilic photocage attached to doxorubicin. The hydrophilic moiety makes the entire prodrug cell impermeable in the dark. Upon irradiation with non-toxic doses of UV light, the photosensitive group is removed and cytotoxic doxorubicin is released into the cells. In the presence of light the IC 50 has been found to be 1.6 ±1.0 μM in JH-Eso-Ad1 cells. The FACS studies further confirmed that the cytotoxicity was due to light triggered release of free doxorubicin from the cell impermeable prodrug. This concept has been further developed by attaching a receptor binding molecule to the photocaged drug to enhance specificity. Specifically, we have attached folic acid and the PSMA binding ligand, DUPA to the photocaged doxorubicin. These targeting groups enable cancer cell selective drug delivery with light. Citation Format: Deboleena Mitra, Martin Michael Dcona, Matthew C.T. Hartman. Photocaged molecules in targeted drug delivery. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4506. doi:10.1158/1538-7445.AM2013-4506