Improving chemotherapy by releasing platinum agents from endolysosomes

Chemotherapeutics remain widely used for the treatment of cancer, and the majority act by causing DNA damage in cancer cells. Many of these are hydrophobic and are taken up by cancer cells through a process called endocytosis. However, such chemotherapeutics may be limited as they are retained in the lysosomes and fail to reach the DNA in the nucleus. Widely-used chemotherapeutics such as bleomycin and gemcitabine are well-known to suffer from this limitation. Other chemotherapeutics such as oxaliplatin are suspected to be similarly limited, yet concrete evidence is lacking. The aim of this proposal is to (1) confirm that oxaliplatin localizes within the endo-lysosomes in cancer cells, and (2) that oxaliplatin can be released by selective destruction of the lysosomes.