Active targeted drug delivery system constructed from functionalized pillararenes for chemo/photodynamic synergistic therapy

Nowadays, although functionalized pillararenes have been widely designed to be used in drug delivery system, targeted group modified pillararenes have been seldom reported and used in tumor multimodal therapy. Herein, a functionalized pillararene with a polyethylene glycol chain and triphenylphosphonium cation WP5-PEG-TPP was designed and synthesized. Subsequently, an active targeted drug delivery system was constructed based on its host-guest interactions with a newly designed porphyrin derivative, Py-Por. The experimental results demonstrated that this drug delivery system has exhibited excellent targeting ability against tumor cells, but interestingly it could not enter normal cells. After loading the hypoxia-activated prodrug tirapazamine, the prepared nanodrugs displayed high lethality to tumor cells due to their chemo/photodynamic synergistic therapy capability, but negligible toxicity to normal cells. Preliminary therapeutic mechanism study elucidated the synergistic therapy process.