Liposomes are extensively used as
drug carriers because of their biocompatibility, low toxicity, and controlled release properties, however challenges exist in the control of their particle size, surface properties and targeting functionality. In this work, we report a
peptide-
lipid nanoparticle platform that can achieve nanoparticle formation, surface functionalization and hydrophobic drug loading in an integrated assembly process. A designer
peptide that harbors bivalent amphipathic α-helices linked by a central loop (ALA
peptide) was used to encapsulate
lipid nanoparticles (LNPs). The bivalency design affords higher
peptide helicity and
lipid-packaging efficiency, and allows encapsulated hydrophobic molecules for more stability under long-term storage. The central loop structure displays sufficient surface exposure as demonstrated by the interaction between
penta-
histidine installed LNPs and Ni-NTA
agarose. RGD-inserted and cytotoxic
iridium complex-encapsulated LNPs showed preferential entry and selective cytotoxicity to
integrin high expression
cancer cells, while showing reduced toxicity to non-
cancer cells. Further study indicates that a constrained cyclic conformation of RGD is required to fully exert targeting capability, suggesting an intact structural exposure on the LNP surface. In summary, we demonstrate a simple yet effective method of
peptide-based LNP surface modification with potential for various targeted deliveries of hydrophobic drugs.