Mitochondrial targeting improves the selectivity of singlet ‐oxygen cleavable prodrugs in NMIBC treatment

Due to higher membrane potential (MMP) of the cancer cells mitochondria ( −220 mV) compared to the MMP in healthy cells (−140 mV), cationic prodrugs are an excellent choice to achieve selectivity. With our singlet oxygen activatable rhodamine linked paclitaxel (Rh-L-PTX) and rhodamine linked SN-38 (Rh-L-SN-38) prodrugs, we could achieve 2–3 times selectivity in  vitro and as much as 34 times selectivity in vivo over non-tumor cells. AbstractMitochondria play an essential role in cancer treatment by providing apoptotic signals. Hexyl aminolevulinate, an FDA-approved diagnosis for non-muscle invasive bladder cancer, induces the production of protoporphyrin IX (PpIX) preferentially by mitochondria in cancer cells. Photosensitizer PpIX upon illumination can release active chemotherapy drugs from singlet oxygen-activatable prodrugs. Prodrugs placed close enough to PpIX formed in mitochondria can improve the antitumor efficiency of PpIX-PDT. The preferred uptake of prodrugs by cancer cells and tumors can further enhance the selective damage of cancer cells over non-cancer cells and surrounding normal tissues. Mitochondriotropic prodrugs of anticancer drugs, such as paclitaxel and SN-38, were synthesized using rhodamine, a mitochondrial-targeting moiety. In  vitro, the mitochondrial targeting helped achieve preferential cellular uptake in cancer cells. In RT112 cells (human bladder cancer cells), intracellular prodrug concentrations were 2–3 times higher than the intr...
Source: Photochemistry and Photobiology - Category: Science Authors: Tags: SPECIAL ISSUE RESEARCH ARTICLE Source Type: research