Fig. 1.

(A) The binding affinity of two somatostatin analogs, octreotide and KE108, to the five subtypes of somatostatin receptors (SSTR 1–5). KE108 displays a high affinity to all five SSTRs, while octreotide only has a high binding affinity to SSTR2 and a moderate affinity to SSTR5. (B) A schematic illustration of the multifunctional unimolecular micelle formed by multi-arm star amphiphilic block copolymer PAMAM–PVL–PEG–OCH₃/Cy5/KE108 for targeted NE cancer therapy. (C) A schematic illustration of the passive and active tumor targeting capabilities exhibited by the multifunctional unimolecular micelles after i.v. injection. Passive tumor targeting is achieved by extravasation of the unimolecular micelles as a result of leaky vessels of the tumor vasculature (i.e., the EPR effect). Active tumor targeting is achieved through the interaction between the KE108 targeting ligands present on the surface of the unimolecular micelles and the SSTRs overexpressed by the NE cancer cells triggering an enhanced cellular uptake of the micelles by the NE cancer cells via receptor-mediated endocytosis.