Pathway-dependent supramolecular polymerization of camptothecin derivatives into filaments for chemotherapy and imaging

Abstract Constructing supramolecular structures via non-covalent interactions depends on the assembly pathway selection, which has attracted much interest in chemistry, materials science, and nanomedicine. Despite recent advances in the formation of a variety of splendid nanostructures in amphiphile assembly, the relationship between the conformation of formed nanostructures and their function (chemotherapy) is less explored, especially in biological systems (i.e., cell and animal). Here we report that nanostructures formed through different assembly pathways of small molecules (i.e., camptothecin derivative) result in distinct cellular distribution and activities toward colon cancer in the cell-based assay and tumor-bearing mouse model. Specifically, conjugation of laminin derivative peptide and hydroxycamptothecin (HCPT) results in nanoparticles with confined conformation, which suppresses the activity of HCPT. The enzyme-instructed polymerization of HCPT-1 results in uniform filaments with an α-helical-like structure, which restores the conformation of laminin derivative peptide and the activity of HCPT both in vitro and in vivo. Replacing HCPT with other functional small molecules also exhibit similar results in our system. This study facilitates the development of functional assemblies with confined conformation for chemotherapy and imaging.