Micelleplex nucleic acid delivery systems: Overcoming barriers for treatment of advanced solid tumors

The activity and longevity of nucleic acids clinical uses are plagued by several barriers, both within and outside cells. Nanomaterials tailored for the transport of nucleic acids are a singular opportunity to overcome these barriers. Among these, polymeric micelles share important attributes that can help achieve efficient translation of RNA-based therapies to the clinic. Such features are self-assembly, ability to micellize, thermodynamic stability, biocompatibility, high exclusion volume, effective condensation and protection of RNA, low toxicity, biological membrane affinity, and facilitation of intracellular transport by endosomal escape mechanisms. Herein, we discuss the latest attempts at delivering a range of nucleic acids using micelles including targeted delivery, improved uptake, prolonged blood circulation, enhanced gene silencing activity, greater cellular adsorption, improved serum stability, enhanced penetration into cancer cells, elevated transfection levels, concurrent delivery of DNA and anti-cancer medications in combination therapy, minimal in vitro cytotoxicity, and adequate protection of nucleic acids from enzymatic digestion. In addition, the diminution of immune stimulation, the reduction of off-target effects, and the improvement of the efficacy and stability of RNA silencing is essential to authenticate nucleic acid molecules as potential treatment targets or therapeutic drugs. Consequently, it is imperative to develop a highly versatile delivery system.