Peptide and nucleic acid-directed self-assembly of cationic nanovehicles through giant unilamellar vesicle modification: Targetable nanocomplexes for in vivo nucleic acid delivery

Abstract

The efficient targeted delivery of nucleic acids in vivo provides some of the greatest challenges to the development of genetic therapies. Giant unilamellar lipid vesicles (GUVs) have been used mainly as cell and tissue mimics and are instrumental in studying lipid bilayers and interactions. Here, the GUVs have been modified into smaller nanovesicles. We have then developed novel nanovesicle complexes comprising self-assembling mixtures of the nanovesicles, plasmid DNA or siRNA, and targeting peptide ligands. Their biophysical properties were studied and their transfection efficiency was investigated. They transfected cells efficiently without any associated cytotoxicity and with targeting specificity, and in vivo they resulted in very high and tumour-specific uptake and in addition, efficiently transfected the lung. The peptide-targeted nanovesicle complexes allow for the specific targeted enhancement of nucleic acid delivery with improved biosafety over liposomal formulations and represent a promising tool to improve our arsenal of safe, non-viral vectors to deliver therapeutic cargos in a variety of disorders.

Liposomal delivery of hydrophobic RAMBAs provides good bioavailability and significant enhancement of retinoic acid signalling in neuroblastoma tumour cells

“…They are suitable for hydrophobic compounds and may also override drug resistance mechanisms [30,31]. Nanoparticles are also known to take advantage of tumour vascular leakiness to more specifically access tumour cells in solid tumours including neuroblastoma [25,28,32]. For RAMBAs, this approach has not been documented to date and we hypothesised that liposomal delivery would improve bioavailability and making such compounds more accessible for use in humans.…”

Hybrid Vesicular Drug Delivery Systems for Cancer Therapeutics

“…Grafting‐from Approach : In the grafting‐from approach, small initiator molecules are linked to a peptide/protein and polymerization is initiated by these macroinitiators . A drawback to this approach is that the polymerization technique should not be allowed to affect the activity of the peptides or the 3D structure of the proteins, which would otherwise lead to a denaturation of the protein . Considering this, Bontempo and Maynard conjugated biotinylated atom transfer radical polymerization (ATRP) to streptavidin (SAv) to develop a protein macroinitiator.…”

“…Tagalakis et al used giant unilamellar vesicle (GUV) precursors and targeting peptides to improve nucleic acid delivery. They demonstrated that biologically safe and stable nanovesicles were produced that were not cytotoxic and did not activate complement systems, unlike usual lipopolyplexes …”

Targeted delivery of HES5-siRNA with novel polypeptide-modified nanoparticles for hepatocellular carcinoma therapy

“…8 The ideal non-viral vector should have the following characteristics: small size below 200 nm, biocompatible, stable enough in blood to protect the nucleic acid, effective delivery of gene into target location, and so on. 9 Selenium (Se) is a mineral trace element of fundamental importance to humans and animals. The role of Se in potential cancer chemotherapeutic and chemopreventive agents has been supported by many epidemiological, preclinical, and clinical studies.…”