antibodies or the known LRP1 ligand receptor-associated protein (RAP) failed to inhibit MoDE 3 mediated uptake of streptavidin in bEnd.3 cells (Figure ). The lack of competition with RAP is consistent with previous results for the delivery of an Angiopep-2 -secretase inhibitor conjugate where RAP competition and LRP1 knock out showed minimal impact on the Angiopep-2 -secretase inhibitor conjugate internalization. To evaluate the role of LRP1 in MoDE 3 mediated uptake of noncovalently bound cargo, we measured streptavidin uptake in the LRP1 + mouse embryonic fibroblast cell line MEF1 and the paired LRP1 knockout cell line PEA13 (Figure ).