The
recent advances in genetic engineering demand the development
of conceptually new methods to prepare and identify efficient vectors
for the intracellular delivery of different nucleotide payloads ranging
from short single-stranded oligonucleotides to larger plasmid double-stranded
circular DNAs. Although many challenges still have to be overcome,
polymers hold great potential for intracellular nucleotide delivery
and gene therapy. We here develop and apply the postpolymerization
modification of polyhydrazide scaffolds, with different degree of
polymerization, for the preparation of amphiphilic polymeric vehicles
for the intracellular delivery of a circular plasmid DNA. The hydrazone
formation reactions with a mixture of cationic and hydrophobic aldehydes
proceed in physiologically compatible aqueous conditions, and the
resulting amphiphilic polyhydrazones are directly combined with the
biological cargo without any purification step. This methodology allowed
the preparation of stable polyplexes with a suitable size and zeta
potential to achieve an efficient encapsulation and intracellular
delivery of the DNA cargo. Simple formulations that performed with
efficiencies and cell viabilities comparable to the current gold standard
were identified. Furthermore, the internalization mechanism was studied
via internalization experiments in the presence of endocytic inhibitors
and fluorescence microscopy. The results reported here confirmed that
the polyhydrazone functionalization is a suitable strategy for the
screening and identification of customized polymeric vehicles for
the delivery of different nucleotide cargos.
Peptide nanotubes are novel supramolecular nanobiomaterials that have a tubular structure. The stacking of cyclic components is one of the most promising strategies amongst the methods described in recent years for the preparation of nanotubes. This strategy allows precise control of the nanotube surface properties and the dimensions of the tube diameter. In addition, the incorporation of 3- aminocycloalkanecarboxylic acid residues in the nanotube-forming peptides allows control of the internal properties of the supramolecular tube. The research aimed at the application of membrane-interacting self-assembled cyclic peptide nanotubes (SCPNs) is summarized in this review. The cyclic peptides are designed to interact with phospholipid bilayers to induce nanotube formation. The properties and orientation of the nanotube can be tuned by tailoring the peptide sequence. Hydrophobic peptides form transmembrane pores with a hydrophilic orifice, the nature of which has been exploited to transport ions and small molecules efficiently. These synthetic ion channels are selective for alkali metal ions (Na(+), K(+) or Cs(+)) over divalent cations (Ca(2+)) or anions (Cl(-)). Unfortunately, selectivity was not achieved within the series of alkali metal ions, for which ion transport rates followed the diffusion rates in water. Amphipathic peptides form nanotubes that lie parallel to the membrane. Interestingly, nanotube formation takes place preferentially on the surface of bacterial membranes, thus making these materials suitable for the development of new antimicrobial agents.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.