Fabrication of Multicomponent Multivesicular Peptidoliposomes and Their Directed Cytoplasmic Delivery

Abstract

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 appears to use different cellular pathways depending on the site of action (i.e., extracellular space or cytoplasm). This study provides the hierarchical peptide-based hMVVs with sophisticated architectures and cell delivery characteristics, thus making a step toward artificial cells or viruses.

Structural control of self-assembled peptide nanostructures to develop peptide vesicles for photodynamic therapy of cancer

“…In contrast, spherical and cylindrical micelles can employ only encapsulation mechanisms for drug loading. In particular, the loading of drugs by the encapsulation mechanism is especially suitable for polymers and peptides because they can form more robust nanoparticles than lipids [ 10 , 11 ]. Given the usefulness of vesicles in drug delivery and the multifunctionality of peptides as supramolecular building blocks, we intend to design and fabricate peptidesomes that can become highly functional nanodrugs in vivo .…”

“…First, peptide building blocks should have a strong propensity to form vesicles rather than other morphologies, which would facilitate performing feedback control of the SPN nanostructural properties by modifying the chemical structures of the peptides. We elected to use cyclic peptides as building blocks because peptides that are both cyclic and amphiphilic have shown a strong tendency to self-assemble into vesicles (peptidesomes) [ 11 ]. Second, the hydrophilic segment of the building blocks would contain a large proportion of arginine residues for the efficient intracellular translocation of SPNs.…”

Physically and Chemically Compartmentalized Polymersomes for Programmed Delivery and Biological Applications

“…(C) Fabrication of the quadruple-hMVV. Reprinted with permission from ref . Copyright 2017 American Chemical Society.…”

“…Contrary to concentric multiwalled vesicles, the walls of the obtained onion-like polymersomes separated by water channels, exhibiting higher drug-loading capacity and stepwise drug-releasing behavior via hydrolytic degradation of the PCL membrane compared to that observed with the single-walled analogue. Moreover, Lim et al 129 reported a self-assembly method for preparing multicomponent and multicompartment polymersomes by multistage selfassembly of peptides and lipid structural units (Figure 20A). The differences of the thermal stability of the building blocks were attributed to the formation of two-component (i.e., peptide and lipid) heteropolyvesicles (hMVVs).…”

“…As one of the most powerful tool to prepare soft nanomaterials with precisely controlled structure and functionality, − polymer self-assembly also plays important role in the fabrication of MCPs, including polymersomes-in-polymersomes, , MVVs, − onion-like polymersomes , and LCVs . For instance, Cheng et al reported the preparation and self-assembly of amphiphilic polyurethane phosphate (PUP), which self-assembled into various morphologies including LCVs by adjusting the hydrophobic chain length and initial polymer concentration in the PU tail.…”