Design of a dendrimer with a matrix metalloproteinase-responsive fluorescence probe and a tumor-homing peptide for metastatic tumor cell imaging in the lymph node

[Display omitted] •A dendrimer imaging agent for metastatic tumor cells in the lymph node was designed.•A carboxy-terminal dendrimer was used as a carrier for delivery to lymph nodes.•A matrix metaloproteinase-2 (MMP-2) responsive fluorescence probe was conjugated.•Modification of a tumor homing peptide, tLyP-1, promoted the uptake of tumor cells.•The dendrimer imaging probe could visualize MMP-2-secreted tumor cells selectively. Fluorescence imaging is a noninvasive technique for cancer diagnosis. Dendrimers are regularly branched macromolecules with highly controllable size and structure that are a potent multifunctional nanoparticle. Anionic-terminal polyamidoamine (PAMAM) dendrimers were previously found to be accumulated in the lymph node, which is one of the main routes of tumor metastasis. In this study, we designed and synthesized a dendrimeric imaging probe for lymph node-resident tumor cell imaging. A matrix metalloproteinase-2 (MMP-2)-responsive fluorescence peptide probe and a tumor-homing peptide were conjugated to the carboxy-terminal dendrimer. The dendrimeric imaging probe treatment showed fluorescence signals inside some tumor cells (e.g., human fibrosarcoma HT-1080 and breast cancer 4T1 cells), depending on the MMP activity, but not in macrophage-like RAW264 cells.