Light induced drug release from a folic acid-drug conjugate.

A major area of cancer research focuses on improving the specificity of therapeutic agents by engineering drug-delivery vehicles that target overexpressed receptors on tumor cells. One of the most commonly used approaches involves targeting of folate receptors using folic acid conjugated to a drug-containing macromolecular cargo. Once internalized via endocytosis, the drugs must be released from these constructs in order to avoid being trapped in the endosomes. Here, we describe the synthesis of a small-molecule conjugate that couples folic acid to doxorubicin via a photocleavable linker. Using HPLC we show that the doxorubicin can be released with light rapidly and with high efficiency. This approach has advantages over macromolecular systems due to its simplicity and efficiency.