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Here, it is shown that self\u2010assembled 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\u2010assembled 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 Self\u2010Assembly \u2010 Glutamic acid, SA\u2010E) demonstrates specific accumulation in various xenograft, syngeneic, patient\u2010derived xenograft, or transgenic rodent models. In addition, SA\u2010E enabled the effective delivery of highly potent chemotherapy to different syngeneic and xenografted tumors with reduced side effects. 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