Roles and applications of peptide nucleic acid-loaded nanoparticles in cancer

Peptide nucleic acid (PNA) is a neutral analogue of DNA/RNA used for diverse antisense and antigene applications. PNA exhibits excellent binding affinity, sequence specificity, resistance to enzymatic degradation, and minimal electrostatic interactions with target oligonucleotides. PNA's potential in therapeutic applications is not fully explored compared to other antisense oligonucleotides (ASOs). PNA designs have been used to target a wide array of microRNAs (miRs) for the potential treatment of various cancers. miRNAs are short, non-coding RNA molecules that regulate post-translational gene expression. In cancer, upregulated miRNA expression plays a crucial role in tumor initiation and progression. The inefficient cellular uptake of PNAs limits their clinical translation. The limitations of PNA prompted the engineering of two classes of nanoparticles (NPs): polymeric-based and silica-based NPs to facilitate the intracellular delivery of PNA in targeted tumor cells and enhance their therapeutic potential in cancer therapy. In this review, we searched the PubMed, Web of Science, and Google Scholar databases, with no publication date restriction, to explore various applications of PNA-loaded nanoparticles in cancer therapy. We have discussed various PNA-loaded nanoparticles used across a range of cancer cell lines and mouse models for cancer therapy.