Host–guest supramolecular approach for the preparation of a ¹⁹ F MRI-guided theranostic agent with long <i>T</i> ₂ relaxation times and its synergetic performances

The construction of highly efficient theranostic materials is critical for accurate lesion diagnosis and treatment. Among various diagnostic modalities, magnetic resonance imaging (MRI) is gaining attention due to its safety and precision. This study presents a novel theranostic agent, TPZ@TSF, that integrates ¹⁹F MRI for diagnostic imaging with photodynamic therapy (PDT) and hypoxia-activated tirapazamine (TPZ) as therapeutic modalities. TPZ@TSF is created through host-guest supramolecular interactions between β-cyclodextrin and adamantane, facilitating the development of complex functional materials. Investigations reveal that TPZ@TSF exhibits substantial intensity amplification in ¹⁹F NMR/MRI when exposed to glutathione (GSH), both <i>in vitro</i> and <i>in vivo</i>, achieving a long <i>T</i>₂ relaxation time of 1267 ms, ensuring its excellent diagnostic profile. <i>In vivo</i>¹⁹F MRI results indicate that TPZ@TSF accumulates in tumors within 8 hours after intravenous administration in mice, providing an ideal timeframe for starting PDT and chemotherapy. Furthermore, therapeutic evaluations suggest that TPZ@TSF enhances chemotherapy efficacy against tumor growth by reducing hypoxia levels through the consumption of oxygen molecules during PDT. This innovative work is anticipated to significantly advance ¹⁹F MRI-guided therapy and improve the development of advanced theranostic agents.