{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:54:15Z","timestamp":1781780055684,"version":"3.54.5"},"reference-count":172,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004564","name":"Ministarstvo Prosvete, Nauke i Tehnolo\u0161kog Razvoja","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Precise regulation of gene expression and drug delivery is required to maximize therapeutic efficacy and minimize adverse side effects. Several studies indicate a potential role for targeted gene and drug delivery in the precision therapy of type 2 diabetes and other diseases. This review summarizes recent knowledge on the cell-penetrating function and membrane-crossing roles of cell-penetrating peptides, the application of peptide nucleic acids for gene modulation, and the precise delivery of genetic material and drugs to insulin signaling and other relevant \u03b2-cell and type 2 diabetes-related genes through antibody\/receptor targeting. The rationale for peptide nucleic acid-based delivery platforms is then reviewed, including their neutral charge, strong hybridization capacity, versatility, and nuclease resistance, These properties enable precise modulation of gene expression in relevant tissues for the treatment of type 2 diabetes. Finally, the review also focuses on the delivery approaches of antibody- and receptor-mediated strategies. These strategies use either whole antibodies or engineered antibody fragments and are typically used to deliver treatments to \u03b2-cells and to cells involved in metabolism.<\/jats:p>","DOI":"10.3389\/fphar.2026.1867532","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T10:25:19Z","timestamp":1781778319000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Enhancing diabetes treatment by targeted nucleic acid and drug delivery using cell-penetrating peptides, peptide nucleic acids, and receptor targeting"],"prefix":"10.3389","volume":"17","author":[{"given":"Bozidarka L.","family":"Zaric","sequence":"first","affiliation":[{"name":"Department of Radiobiology and Molecular Genetics, VIN\u010cA Institute of Nuclear Sciences \u2013 National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Khodahemmati","sequence":"additional","affiliation":[{"name":"Department of Radiobiology and Molecular Genetics, VIN\u010cA Institute of Nuclear Sciences \u2013 National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja S.","family":"Zafirovic","sequence":"additional","affiliation":[{"name":"Department of Radiobiology and Molecular Genetics, VIN\u010cA Institute of Nuclear Sciences \u2013 National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esma R.","family":"Isenovic","sequence":"additional","affiliation":[{"name":"Department of Radiobiology and Molecular Genetics, VIN\u010cA Institute of Nuclear Sciences \u2013 National Institute of the Republic of Serbia, University of Belgrade","place":["Belgrade, Serbia"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.jconrel.2006.09.011","article-title":"Vectorization of morpholino oligomers by the (R-Ahx-R)4 peptide allows efficient splicing correction in the absence of endosomolytic agents","volume":"116","author":"Abes","year":"2006","journal-title":"J Control Release"},{"key":"B2","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1016\/j.jconrel.2005.10.026","article-title":"Endosome trapping limits the efficiency of splicing correction by PNA-oligolysine conjugates","volume":"110","author":"Abes","year":"2006","journal-title":"J Control. 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