(658e) Development of a Supermolecular Complex for Selective Sensing and Targeting By Surface Engineering of Poly(amido amine) Dendrimers With a Thin Layer of Zwitterionic Carboxybetaine and c(RGDyK) Motifs

To realize protein-like selective targeting, a new group of nano supermolecular complexes was prepared. This new complex consists of a protein-mimicking zwitterionic shell formed by a thin and dense layer of (3-acryloylamino-propyl)-(2-carboxy-ethyl)-dimethyl-ammonium (CBAA) immobilized at primary amine groups of poly(amido amine) (PAMAM) dendrimers of generation 5 (G5), an encapsulated fluorescein sodium in the core of CBAA-modified PAMAM G5 for molecular tracing, and various numbers of conjugated cyclic Arg-Gly-Asp-d-Tyr-Lys [c(RGDyK)] peptides at primary amine groups of PAMAM G5 for selective targeting. The nano supermolecular complexes exhibit 1 to 2 orders higher binding affinity to integrin than c(RGDyK) peptide alone in both phosphate buffered saline (PBS) and fetal bovine serum (FBS), while the high selectivity of c(RGDyK) peptide could be preserved. Moreover, the carrier of c(RGDyK) peptides, CBAA-modified PAMAM G5, is fully biocompatible through successful minimizing the strongly nonspecific interaction of –NH₂ termini of PAMAM G5 with proteins and cell membranes by the strong hydrated zwitterionic layer of CBAA. These results demonstrated that we can improve the affinity of targeting motifs without clear interference in the selectivity through fine-tuning protein-like molecular architecture.