Fabrication of Multicomponent Multivesicular Peptidoliposomes and Their Directed Cytoplasmic Delivery

A novel self-assembly strategy for the formation of multicomponent and multicompartment vesicles via the hierarchical assembly of the cyclic peptide and lipid building blocks is reported. The primary driving force underlying the formation of dual-component (i.e., peptide and lipid) heteromultivesicular vesicles (hMVVs) is the differential thermostability between the supramolecular building blocks. Furthermore, the combination of the differential thermostability and charge-based separation further enables the fabrication of the hMVVs that incorporate up to four different components (i.e., two different building blocks and two different encapsulated molecules). The quadruple-component hMVVs consist of cyclic peptides, lipids, negatively charged green fluorescent probes (GFPr), and positively charged red fluorescent probes (RFPr). Intracellular delivery study shows that cellular localization of hMVVs is directed by the function of hMVV envelopes, and the nuclear localization signal (NLS) of peptide vesicles ...