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Review
. 2025 Jun 17;31(34):e202500469.
doi: 10.1002/chem.202500469. Epub 2025 May 21.

Recent Cutting-Edge Technologies for the Delivery of Peptide Nucleic Acid

Concetta Avitabile  1 , Maria Teresa Cerasa  2   3 , Antonia D'Aniello  1 , Michele Saviano  1 , Maria Moccia  3
Affiliations
Review

Recent Cutting-Edge Technologies for the Delivery of Peptide Nucleic Acid

Concetta Avitabile et al. Chemistry. .

Abstract

Peptide nucleic acids (PNAs) have garnered significant attention due to their enhanced chemical, physical, and binding properties in comparison to natural nucleic acids. This prompted their application in antigene/antisense approach, assigning them a pivotal role in gene editing and, more recently, showing their potential as "bilingual" molecules being able "to speak" both nucleic acid and protein language. However, to expand the applications of PNAs in therapy, the challenge of effectively delivering PNAs to cells needs to be addressed. Among several delivery approaches employed so far, the nanotechnology-based ones showed great potential. In this review, we provide an overview of the latest in the field (2019 to present), beginning from peptide-based delivery systems, as well as cutting-edge approaches involving nanoparticles, liposomes, and calixarene, showing how they have inspired the development of smarter delivery approaches to boost PNAs applications.

Keywords: calixarene; delivery systems; liposomes; nanoparticles; peptides.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
a) Chemical structures of PNA, DNA, and RNA, b) PNA‐DNA/RNA recognition mode.
Figure 2
Figure 2
Method for the uptake of PNA into the cell: a) unmodified PNA; b) technologies for PNA delivery (electroporation, sonoporation, microinjection); c) backbone‐modified PNA; d) passive diffusion; e) endocytosis; f) receptor‐mediated uptake.
Figure 3
Figure 3
a) PNA‐modified backbone; b) PNA R monomer.
Figure 4
Figure 4
Sequence of PNA1, PNA 6, PNA 7, and PNA 9.
Figure 5
Figure 5
Sequence of GalNAc3‐PNA 2 and [Cγ(S)‐GalNAc‐T]3‐PNA 3; structures adapted from ref. [38, 40].
Figure 6
Figure 6
a) Ser‐PNA and Arg‐PNA; b) D‐monomer and Cp‐monomer; c) thyclotide.
Figure 7
Figure 7
Nanoparticle properties.
Figure 8
Figure 8
HNTs‐based PNA‐delivery system.
Figure 9
Figure 9
Various applications of gold nanoparticles.
Figure 10
Figure 10
PNA‐PEGylated GO cellular uptake.
Figure 11
Figure 11
a) Depiction of a PNA oligomer linked to amino acid residues with different charges; b) Scheme of the calcium silicate trapping method for producing PNA‐loaded pSiNPs.
Figure 12
Figure 12
Multifunctional mesoporous silica nanoparticles.
Figure 13
Figure 13
Scheme of a molecularly targeted stealth PLGA‐NP.
Figure 14
Figure 14
Liposomes for drug delivery.
Figure 15
Figure 15
Scheme of bicelle structure.
Figure 16
Figure 16
a) Calixarene‐derived inclusion complexes; b) Calixarene system employed for PNA delivery.
See this image and copyright information in PMC

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