Abstract

The interactions of nanomaterials with biomolecules in vivo determine their biological fate. Here, we show that self-assembled peptide amphiphile (PA) nanostructures can dynamically interact with endogenous biomolecules and take advantage of naturally occurring processes to target a broad range of solid tumors. In circulation, self-assembled PA nanostructures disassemble and reassemble mainly with lipoproteins, which prolongs blood circulation and dramatically improves tumor accumulation and retention. Mechanistic studies suggested that PAs internalize into cancer cells by assembling with their cell membranes and independently of specific receptors. By exploiting these interactions, a PA developed in this study (namely SA-E) demonstrated specific accumulation in various xenograft, syngeneic, patient-derived xenograft, or transgenic rodent models. In addition, SA-E enabled the effective delivery of highly potent chemotherapy to different syngeneic and xenografted 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.