Advances in Nucleic Acid Delivery Using Nanocarriers for Gene Therapy in Cancer: A Narrative Review.

Cancer remains a leading cause of morbidity and mortality worldwide, underscoring the need for innovative and targeted treatment strategies. Gene therapy, particularly via nucleic acid-based therapeutics such as siRNA, miRNA, mRNA, plasmid DNA, and antisense oligonucleotides, has emerged as a promising approach to selectively modulate oncogenic pathways, restore tumor suppressor functions, and enhance anti-tumor immunity. However, clinical translation of these therapies is significantly hindered by biological barriers including nuclease degradation, poor cellular uptake, immune activation, and off-target effects. To address these challenges, a diverse range of nanocarrier platforms comprising lipid-based nanoparticles, polymeric carriers, inorganic nanostructures, and biomimetic cell-membrane-coated systems have been developed to improve the stability, bioavailability, and tumor specificity of nucleic acid delivery. These nanocarriers can be engineered for passive targeting through the enhanced permeability and retention (EPR) effect, or for active targeting via surface functionalization with ligands such as antibodies, peptides, or aptamers. Furthermore, stimuli-responsive designs enable controlled release of genetic payloads within the tumor microenvironment, enhancing therapeutic precision. The convergence of nanotechnology and gene therapy not only offers potential solutions to drug resistance and tumor heterogeneity but also supports the development of multifunctional theranostic platforms capable of simultaneous treatment and real-time imaging. This narrative review explores the advances in nanocarrier-mediated delivery systems for nucleic acid-based cancer therapies, highlighting their design principles, targeting strategies, and therapeutic applications across solid and hematologic malignancies. Collectively, these innovations hold promises for transforming cancer care toward more effective, personalized, and minimally invasive treatment paradigms.