Peptide Amphiphiles Hitchhike on Endogenous Biomolecules for Enhanced Cancer Imaging and Therapy

The interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, we show that a self-assembled peptide amphiphile nanostructure (namely SA-E) dynamically interacts with endogenous biomolecules and takes advantage of naturally occurring processes to target a broad range of solid tumors. Upon in vivo administration, self-assembled nanostructures of SA-E disassemble and reassemble with lipoproteins in circulation. Hitchhiking on lipoproteins prolongs the blood circulation of SA-E and allows it to cross endothelial barriers through transcytosis. At the tumor site, SA-E internalizes into cancer cells by mainly interacting with lipid-raft domains on cell membranes. By exploiting these endogenous interactions, SA-E demonstrated high tumor accumulation with extended retention in various xenograft, syngeneic, patient-derived xenograft, or transgenic mouse and rat models. In addition, SA-E enabled the effective delivery of highly potent chemotherapy to breast and glioma tumors with reduced side effects. With its simple and modular design and universal tumor accumulation mechanism, SA-E represents a promising platform for broad applications in cancer imaging and therapy. ### Competing Interest Statement The authors have declared no competing interest.