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Structure of ACPPs and ACPPDs. While the cleavage sequences (green) between the polyanion (Suc(glu)8, red) and polycation ((arg)9, blue) of ACPP (top row) or ACPPD (bottom row) remain intact, the ACPP(D) remains nonadherent due to the masking of (arg)9. Once MMP-2/-9 cleaves the linkers, the polyanions are released, allowing the polycations and their payloads (Cy5 and Gd) to adhere to cells and become endocytosed. Only nine out of approximately 30 Gd-DOTA are depicted in ACPPDs.
