Photostable rubyrins bearing pentafluorophenyl pendants for enhanced reactive oxygen species generation using an 808 nm laser

Abstract

Organic photosensitizers with long-wavelength absorption, photostability and tumour specificity are highly desired in photodynamic therapy (PDT), but the molecular design for this three-in-one formula is quite challenging. Herein, we report the molecular engineering of a series of expanded porphyrinoids with N-anisyl dithienopyrrole (DTP) and meso-pentafluorophenyl substituents to collectively accelerate the reactive oxygen species (ROS) generation. Due to extensive π-conjugation, the Q-bands are significantly red-shifted, extending into the near-IR region. Hence, this series of molecules can be photoactivated using the deeply penetrating 808 nm laser. Interestingly, subtle tuning of singlet oxygen production could be achieved by increasing the number of meso-pentafluorophenyl pendants. This was corroborated via photophysical and theoretical studies, which suggested altered electron distribution and stabilization of energy levels for rubyrins with four pentafluorophenyl substituents. On the contrary, heptaphyrin with its increased π-electrons exhibited no ROS generation due to the mismatch in energy gap with molecular oxygen. The photodynamic properties of these macrocycles and their respective nanoparticles, including their remarkable ROS generation, exceptional photostability and biocompatibility, demonstrate their potential as excellent candidates for PDT. The in vitro experiments substantiate the effective anticancer activity of these nanoparticles, offering future potential opportunities for application via in vivo PDT and bioimaging.