Far-Red Light-Activatable Prodrug of Paclitaxel for the Combined Effects of Photodynamic Therapy and Site-Specific Paclitaxel Chemotherapy

Paclitaxel
(PTX) is one of the most useful chemotherapeutic agents
approved for several cancers, including ovarian, breast, pancreatic,
and nonsmall cell lung cancer. However, it causes systemic side effects
when administered parenterally. Photodynamic therapy (PDT) is a new
strategy for treating local cancers using light and photosensitizer.
Unfortunately, PDT is often followed by recurrence due to incomplete
ablation of tumors. To overcome these problems, we prepared the far-red
light-activatable prodrug of PTX by conjugating photosensitizer via
singlet oxygen-cleavable aminoacrylate linker. Tubulin polymerization
enhancement and cytotoxicity of prodrugs were dramatically reduced.
However, once illuminated with far-red light, the prodrug effectively
killed SKOV-3 ovarian cancer cells through the combined effects of
PDT and locally released PTX. Ours is the first PTX prodrug that can
be activated by singlet oxygen using tissue penetrable and clinically
useful far-red light, which kills the cancer cells through the combined
effects of PDT and site-specific PTX chemotherapy.