One- and Two-Photon Activated Release of Oxaliplatin from a Pt(IV)-Functionalized Poly(phenylene ethynylene)

We report a water-soluble poly­(phenylene ethynylene) (PPE-Pt­(IV)) that is functionalized with oxidized oxaliplatin Pt­(IV) units and its use for photoactivated chemotherapy. The photoactivation strategy is based on photoinduced electron transfer from the PPE backbone to oxaliplatin Pt­(IV) as an electron acceptor; this process triggers the release of oxaliplatin, which is a clinically used anticancer drug. Mechanistic studies carried out using steady-state and time-resolved fluorescence spectroscopy coupled with picosecond–nanosecond transient absorption support the hypothesis that electron transfer triggers the drug release. Photoactivation is effective, producing oxaliplatin with a good chemical yield in less than 1 h of photolysis (400 nm, 5 mW cm–2). Photorelease of oxaliplatin from PPE-Pt­(IV) can also be effected with two-photon excitation by using 100 fs pulsed light at 725 nm. Cytotoxicity studies using SK-OV-3 human ovarian cancer cells demonstrate that without photoactivation PPE-Pt­(IV) is not cytotoxic at concentrations up to 10 μM in polymer repeating unit (PRU) concentration. However, following a short period of 460 nm irradiation, oxaliplatin is released from PPE-Pt­(IV), resulting in cytotoxicity at concentrations as low as 2.5 μM PRU.