Mitochondria-targeting and ROS-sensitive smart nanoscale supramolecular organic framework for combinational amplified photodynamic therapy and chemotherapy

Owing to their reversibly dynamic features, and the regularity of their architectures, supramolecular organic frameworks (SOFs) have attracted attention as new porous materials. Herein, we propose a smart SOF platform for enhanced photodynamic therapy, where the SOF with a superior mitochondria-targeting capability could be cleaved by reactive oxygen species (ROS) produced by itself for highly enhancing PDT. Moreover, it can further work as a platform for carrying chemo-therapeutic drug doxorubicin for synergistic chemo-photodynamic therapy. The SOF is constructed by combining a tetra- beta-cyclodextrin-conjugated porphyrin photosensitizer and a ROS-sensitive thioketal linked adamantane dimer utilizing a host-guest supramolecular strategy. The unique supramolecular framework not only completely resolves the aggregation caused quenching of porphyrin photosensitizers but also endows them with significantly enhanced water-solubility. The in vitro and in vivo results demonstrate that the SOF could be targeted onto mitochondria by confocal imaging, and dissociated by ROS generated by itself, leading to autonomous release of porphyrin photosensitizers and DOX for high anti-cancer activity. It is believed that the strategy using a SOF has the potential of being used to construct versatile agents for combined therapies.

Automated summary

A smart SOF platform has been proposed for enhanced photodynamic therapy, targeting mitochondria and releasing photosensitizers and DOX autonomously for high anti-cancer activity. The unique supramolecular framework solves aggregation-caused quenching of photosensitizers and enhances their water-solubility, showing potential for versatile agents in combined therapies.