Enhancing diabetes treatment by targeted nucleic acid and drug delivery using cell-penetrating peptides, peptide nucleic acids, and receptor targeting.

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 β-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 β-cells and to cells involved in metabolism.