Self-Assembly Mediated Platform for Rapid and Facile Preparation of Peptide-Functionalized Nanoparticles with High Stability

Abstract

We recently reported a two-component self-assembling system, where the core of nanoparticles (NPs) was first assembled by a simple triskelion Fmoc-conjugate (FTAEA) and then stabilized by an oligopeptide, Fmoc-FY. Here we showed that the two-component NPs were stable upon heating, incubation, and dilution. We expanded the oligopeptides suitable for stabilization and therefore allowed peptides to serve the dual role of stabilization and functionalization. Twelve molecules were systematically designed and tested to define the design criteria of oligopeptide stabilizers, which are summarized as follows: 1) carrying Fmoc headgroup to match with the aromatic groups on the NP core, 2) restricting the first amino acid to those with self-interacting side chains, and 3) the net charge of the hydrophilic oligopeptide sequence being negative. To validate these criteria, we designed two bioactive peptides, Fmoc-FC and Fmoc-FRGD, which were demonstrated to be capable of stabilizing FTAEA NPs. The bioactivity of the peptide was illustrated with Nile red-loaded Fmoc-FRGD stabilized NPs of around 70 nm in diameters. These NPs were differentially internalized by MDA-MB-435 human cancer cells compared to NPs stabilized with the scrambled sequence, Fmoc-FRDG. Our results here showed that the stepwise aromatic-driven self-assembly provided a facile and versatile approach to construct functionalized and bioactive NPs, which are expected to find applications in drug delivery and bioimaging