Functionalization of silica nanoparticles for nucleic acid delivery

Silica nanoparticles (SiNPs) have been widely engineered for biomedical applications, such as bioimaging and drug delivery, because of their high tunability, which allows them to perform specific functions. In this review, we discuss the functionalization and performance of SiNPs for nucleic acid delivery. Nucleic acids, including plasmid DNA (pDNA) and small interfering RNA (siRNA), constitute the next generation molecular drugs for the treatment of intractable diseases. However, their low bioavailability requires delivery systems that can circumvent nuclease attack and kidney filtration to ensure efficient access to the target cell cytoplasm or nucleus. First, we discussed the biological significance of nucleic acids and the parameters required for their successful delivery. Next, we reviewed SiNP designing for nucleic acid delivery with respect to nucleic acid loading and release, cellular uptake, endosomal escape, and biocompatibility. In addition, we discussed the co-delivery potential of SiNPs. Finally, we analyzed the current challenges and future directions of SiNPs for advanced nucleic acid delivery.