Peptide Nanovesicles Formed by the Self-Assembly of Branched Amphiphilic Peptides

Abstract

Peptide-based packaging systems show great potential as safer drug delivery systems. They overcome problems associated with lipid-based or viral delivery systems, vis-a-vis stability, specificity, inflammation, antigenicity, and tune-ability. Here, we describe a set of 15 & 23-residue branched, amphiphilic peptides that mimic phosphoglycerides in molecular architecture. These peptides undergo supramolecular self-assembly and form solvent-filled, bilayer delimited spheres with 50–200 nm diameters as confirmed by TEM, STEM and DLS. Whereas weak hydrophobic forces drive and sustain lipid bilayer assemblies, these all-peptide structures are stabilized potentially by both hydrophobic interactions and hydrogen bonds and remain intact at low micromolar concentrations and higher temperatures. A linear peptide lacking the branch point showed no self-assembly properties. We have observed that these peptide vesicles can trap fluorescent dye molecules within their interior and are taken up by N/N 1003A rabbit lens epithelial cells grown in culture. These assemblies are thus potential drug delivery systems that can overcome some of the key limitations of the current packaging systems.

Self-assembling peptide-based building blocks in medical applications

“…In addition to the previous sequence, the amphiphilic peptide sequence was obtained with C-terminus attachment of two hydrophobic adhesive sequences, FLIVIGSII and FLIVI, in a parallel array into branched structures with predetermined amino acids, resulting in self-assembly towards solvent-filled bilayered vesicles with 50–200 nm range [110] (Figure 4). The in vitro studies showed the cellular uptake of vesicles, their accumulation within the perinuclear space membrane, and their potential for encapsulating larger molecules such as hydrophilic drugs, peptides, proteins and large plasmids [110].…”

“…The in vitro studies showed the cellular uptake of vesicles, their accumulation within the perinuclear space membrane, and their potential for encapsulating larger molecules such as hydrophilic drugs, peptides, proteins and large plasmids [110]. …”

Branched Amphiphilic Cationic Oligopeptides Form Peptiplexes with DNA: A Study of Their Biophysical Properties and Transfection Efficiency

“…After de-protection of the side chain amino group of the lysine using 80% TFA in dichloromethane chloride (DCM); the N-Hydroxysuccinimide ester of the 5/6-carboxy-tetramethyl rhodamine was used to couple the dye to the ε-amino site of a lysine residue in the presence of 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 7 N,N-Diisopropylethylamine (DIEA). The remainder of the synthesis was carried out as previously detailed 22 .…”

“…Recently, we reported results on a set of peptides that self-assemble to form stable nanocapsules 22 with lipid-like properties 23 . The Branched Amphiphilic Peptides Capsules, termed BAPCs are able to encapsulate, retain and deliver (in vitro) a variety of solutes into cells, including the alpha-emitting 225 Actinium and its radioactive daughter radionuclides 24 .…”

The effect of pH and calcium ions on the stability of amphiphilic and anionic β‐sheet peptide hydrogels

“…Amphiphilic peptides that tend to adopt the b-sheet structure have been shown to assemble into various nanoscale morphologies, such as fibrils, nanotubes and liposomes. [9][10][11] Amphiphilic peptides can also be directed to form hydrogels composed of elongated fibril assemblies with widths in the nanometer range. 1,7,8,12 These self-assembled peptide matrices have been shown to function as drug delivery systems and as scaffolds that mimic extracellular matrices, useful for tissue regeneration purposes.…”