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. In other embodiments, a 
cell surface 
receptor ligand is coupled to a lipid anchor and is displayed on the surface of the HPPS nanoparticles by incorporation of the lipid anchor into the phospholipids 
monolayer of the HPPS 
nanoparticle. The present invention also provides pharmaceutical formulations comprising HPPS nanoparticles and methods of making the HPPS nanoparticles.