Harnessing\nCross-strand π–π Interlocking\nfor Synergistic Enhancement of Immune Checkpoint Blocking and Ferroptosis

The dynamic nature of noncovalent bonds in peptide self-assembly\nallows for selective accommodation of guest molecules. However, it\nremains unclear how to harness coassembly to reinforce the host peptides\nand simultaneously improve the application defects of guest molecules.\nThis study aims to achieve supramolecular synergy between the host\nand guest, further expanding the functional space of the hybrid nanostructures.\nHerein, we utilized the aromatic regions present in β-sheet\npeptides to accommodate aromatic molecules, forming long-range nanotubes\n(NQ40@AIF) through a unique ‘cross-strand π–π\ninterlocking’. This strategy not only stabilizes the coassembly\neffectively but also synergizes the biological functions of the host\nand guest molecules. Moreover, due to the chemical diversity of the\ncoassembled NQ40@AIF, it exhibits advantages in tumor combination\ntherapy, achieving effective synergy between ferroptosis and immune\ncheckpoint blocking. This work provides a minimalistic strategy for\nconstructing peptide nanostructures with complex functionalities.