Lactate-depleted pillar[5]arene-based chiral supramolecular nanovesicles for <scp>l</scp>-glucose-mediated tumor-specific chemodynamic- and photodynamic-synergistic therapy

The distinct interactions of D/L-glucose with cells and biological systems have garnered significant attention. However, the impact of chiral glucose-modified nanomaterials on cancer diagnosis and treatment remains largely unexplored. Here, based on the host-guest interaction between D-/L-glucose-modified pillar[5]arene (D-/L-CP5) serving as the host molecule and Fe-porphyrin derivatives (FeTPPNHC) acting as the guest, an acid-responsive chiral supramolecular vesicle was constructed for transporting lactate oxidases (LOx) (denoted as LOx@D-/L-CP5⊃FeTPPNHC), aiming to enhance chirality-mediated tumor-specific cascade chemodynamic therapy (CDT) and photodynamic therapy (PDT) through the depletion of lactic acid (LA). Surprisingly, the L-glucose-mediated chiral vesicles exhibit remarkable chirality recognition and lactate depletion capabilities, which were higher than the D-glucose-mediated chiral vesicles. Once internalized by cancer cells, L-supramolecular nanomicelles can directly consume LA to generate a considerable amount of H₂O₂, which can then be converted into ˙OH and ¹O₂. <i>In vitro</i> and <i>in vivo</i> studies demonstrate the high tumor specificity and therapeutic efficacy of LOx@LCP5⊃FeTPPNHC. The findings suggest that chiral glucose-modified nanomaterials hold great potential in targeted cancer treatment, paving the way for the development of innovative cancer therapeutics based on their unique interactions with biological systems.