Abstract
The number of applications of peptide nucleic acids (PNAs)—oligonucleotide analogs with a polyamide backbone—is continuously increasing in both in vitro and cellular systems and, parallel to this, delivery systems able to bring PNAs to their targets have been developed. This review is intended to give to the readers an overview on the available carriers for these oligonucleotide mimics, with a particular emphasis on newly developed multi-component- and multifunctional vehicles which boosted PNA research in recent years. The following approaches will be discussed: (a) conjugation with carrier molecules and peptides; (b) liposome formulations; (c) polymer nanoparticles; (d) inorganic porous nanoparticles; (e) carbon based nanocarriers; and (f) self-assembled and supramolecular systems. New therapeutic strategies enabled by the combination of PNA and proper delivery systems are discussed.
Highlights
It is clear that the possible success of the most promising applications of peptide nucleic acids (PNAs)-based technologies strongly depends on the effectiveness of their delivery to the target organs or cell-type, both in terms of internalization and of localization in the proper cellular compartment
Octa-arginine PNAs showed good activity against different type of microRNAs in proper cell cultures, such as miR-145 and miR-221. In the former case, the inhibition of the biological target led to an increased expression of the cystic fibrosis conductance regulator (CTFR) in Calu-3 cells [89], while in the latter example the sequestration of the given miR promoted a higher expression of the p27Kip1 gene in the breast cancer MDA-MB-231 line [90]. Both octa-arginine and tetralysine tails were instead found to induce a PNA-mediated decrease of hepatitis B virus replication after intravenous administration in ducklings, with better results in terms of sequence selectivity when the polylysine moiety was conjugated to the given antisense oligomer [91,92]
Other naturally occurring materials have been used to attempt the intracellular delivery of PNAs, including chitosan, a copolymer composed by glucosamine and N-acetyl glucosamine that can be obtained by deacetylation of chitin [166]
Summary
Peptide nucleic acids (PNAs, Figure 1) are DNA analogues in which the sugarphosphate units connecting the nucleobases are replaced by N-(2-aminoethyl)glycine moieties [1]. We will focus only on the applications of diagnostics in which PNA probes are delivered into cells (in vitro or in vivo detection), leaving to the readers some general review for their use in the sensory sector [17,18] Another application of PNAs which has recently attracted increasing attention is their use as “smart” materials for self-assembly, nanofabrication, and computing, as they are able to form PNA:PNA duplexes which can be modulated in stability and helical handedness [18,19,20].
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