Multifunctional polymeric micelle-based nucleic acid delivery: Current advances and future perspectives

Abstract Nucleic acid (NA) therapeutics are a rapidly growing class of biomedicines with the ability to manipulate gene expression in potent and specific manner, and with the enormous potential in the treatment of life-threatening diseases. Sensibility towards physiological barriers that compromises their therapeutic applicability led to design of highly functional polymeric micelles (PMs). PMs constitute colloidal polymer-based core-shell structures composed of amphiphilic building blocks, serving as efficient NA delivery platforms based on their ability to accommodate NAs mainly through electrostatic-driven complexation processes. Facile manipulation of polymeric building blocks offers the possibility to tune crucial parameters indispensable for NA protection and efficacious delivery to targeted sites. Ordered core-shell structure enables incorporation of other therapeutic/diagnostic agents, presenting possibility for combined therapy and theranostics. In this review we highlight design, characterization, major developments and latest applications of PMs, and provide a critical overview of current challenges and future prospects of PMs as potential NA-based delivery systems aimed at improved NA therapies.