A Dense Layer of Polyethyleneglycol and Zwitterionic Bone Targeting Peptide on the Surface of Stereocomplex Polylactide-Polyethyleneglycol Nanoparticles Improves Shelf-storage Stability and the Serum Compatibility.

The surface properties of nanoparticles (NPs) affect their stability and formation of the protein corona, which influence their targeting abilities. We evaluated these properties using bone (hydroxyapatite; HAP) targeting peptide on tamoxifen (TAM)-loaded stereocomplexformed polylactide-polyethyleneglycol (SC-PLA-PEG) NPs. Octaaspartic acid-octaglycine-cysteine (D8G8C) anionic derivative (Ani. pep.) and octa-aspartic acid-octa lysine-cysteine (D8K8C), a zwitterionic derivative (Zwi. pep.) were conjugated with SC-PLA-PEG NPs as HAP-targeting peptides. The addition of hydrophobic PLA homopolymers increased the surface PEG density on the NPs. Denser PEG chains on NPs decreased their specific surface area, reducing protein adsorption on the NPs and TAM release from NPs. NPs with dense PEG chains and Zwi. pep. showed superior shelf stability and lower protein adsorption than NPs with dense PEG chains and Ani. pep. in murine serum. Furthermore, the HAP-binding ability of NPs with Zwi. pep. was significantly higher than that of NPs with Ani. pep. These results indicate that decreasing the specific surface area and zwitterionization of HAP-targeting peptides on NPs are promising approaches to improve the serum compatibility and stability of NPs.