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

Sushanth Gudlur,Pinakin Sukthankar,L Adriana Avila,John M Tomich,Takeo Iwamoto,Jianhan Chen,Jian Gao,Yasuaki Hiromasa,Maria Gasset

doi:10.1371/journal.pone.0045374

Sushanth Gudlur, Pinakin Sukthankar + Show 7 more

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https://doi.org/10.1371/journal.pone.0045374

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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.

Highlights

Lipid-based carriers such as liposomes and micelles have traditionally been the preferred methods of choice for delivering bioactive compounds into living systems [1]
Polymeric vesicles can be obtained from a variety of self-assembling molecules [12,13,14,15,16,17] of which, vesicles assembled from amphiphilic block copolymers are the most widely studied
While block copolymer monomers composed entirely of polypeptides, like AcVmKn-NH2, Ac-GmDn-OH, Ac-V6D-OH, Ac-KA6-OH have been reported to form vesicles, these examples are only a few when compared to the many synthetic polymers that are capable of self-assembling into vesicles

Summary

Introduction

Lipid-based carriers such as liposomes and micelles have traditionally been the preferred methods of choice for delivering bioactive compounds into living systems [1]. Recent research on self-assembling polymeric vesicles show promise in replacing liposomes and other lipid-based delivery systems as a means for targeting cells or tissues [12]. While block copolymer monomers composed entirely of polypeptides, like AcVmKn-NH2, Ac-GmDn-OH, Ac-V6D-OH, Ac-KA6-OH have been reported to form vesicles, these examples are only a few when compared to the many synthetic polymers that are capable of self-assembling into vesicles. Vauthey et al (2002) [18] were the first to show that a simple 7–8 residue amphiphilic peptide is capable of self-assembling into nanotubes and nanovesicles. Van Hell et al (2007) [20], showed the self-assembly of an amphiphilic oligopeptide SA2 into a nano-sized vesicle These vesicles carry the advantage of being more biocompatible and biodegradable than other synthetic and semi-synthetic polymer vesicles, but are more stable than lipid and polysaccharide vesicles. Excellent reviews on polymeric vesicles and self-assembly of peptide amphiphiles discuss the various facets of such supramolecular assembly [12,13,21,22,23]

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