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.
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