Different functionalized nanocarriers for improvement of gene delivery

Abstract

Gene delivery is a highly advanced therapeutic approach that involves introducing of therapeutic nucleic acids, including DNA and RNA, into target cells to restore, regulate, or enhance cellular function. Delivery vectors are a critical determinant of gene therapy efficacy and are generally classified as either viral or non-viral. Viral vectors are often transfection-efficient, but the clinical applications are limited by concerns such as immunogenicity, limited cargo capacity, and manufacturing complexity. In contrast, non-viral vectors offer greater safety, structural versatility, and ease of production but often have lower delivery efficiency and encounter various extracellular and intracellular barriers. Recent advances in nanotechnology have enabled the development of a variety of nanocarriers that can partially overcome these limitations and improve of gene transfer performance. Protection of nucleic acids from degradation, selective delivery to target cells with minimal uptake by healthy tissues, efficient cellular internalization and intracellular release of the genetic cargo are among the major challenges in gene delivery. Functionalization of nanocarriers is a promising strategy to overcome these barriers, enhancing nucleic acid loading, colloidal stability, biocompatibility, targeting ability, endosomal escape, and overall transfection efficiency. This review summarizes various functionalized nanocarriers for gene delivery including silica-based nanoparticles (NPs), gold NPs, magnetic NPs, graphene-based materials, carbon nanotubes, polycationic systems, and lipidic nanostructures. Special emphasis is placed on the role of surface functional groups and ligands in modulating biological performance and overcoming delivery barriers. The studies reviewed here all show that functionalized nanocarriers are generally better than their non-functionalized counterparts. However, their effectiveness strongly depends on the composition of the nanocarrier, the surface chemistry, the nature of the cargo, and the context of the target cell. Overall, functionalized nanostructures are promising platforms for improving the safety and efficiency of non-viral gene delivery.