Abstract: The present invention provides a non-naturally occurring High-Density Lipoprotein-like peptide-phospholipid scaffold (“HPPS”) nanoparticle. More particularly, the invention provides a non-naturally occurring peptide-lipid nanoscaffold comprising: (a) at least one phospholipid; (b) at least one unsaturated lipid, preferably an unsaturated sterol ester, further preferably an unsaturated cholesterol ester, further preferably cholsteryl oleate; and (c) at least one peptide, the peptide comprising an amino acid sequence capable of forming at least one amphipathic a-helix; wherein the components a), b) and c) associate to form the peptide-phospholipid nanoscaffold. In embodiments of the present invention, a cell surface receptor ligand is incorporated into the HPPS. In one embodiment, the cell surface receptor ligand is covalently bonded to the peptide scaffold of the HPPS nanoparticles.