Tuning the Size, Shape, and Structure of RNA Nanoparticles for Favorable Cancer Targeting and Immunostimulation 1

Abstract

The past decade has shown exponential growth in the field of RNA nanotechnology. The rapid advances of using RNA nanoparticles for biomedical applications, especially targeted cancer therapy, suggest its potential as a new generation of drug. Following the first milestone of chemical drugs and the second milestone of protein drugs in drug development, it has been predicted that the third milestone will be RNA drugs that can be either RNA itself as drugs or chemicals/ligands that target RNA. Thus, a comprehensive assessment of the current therapeutic RNA nanoparticles is urgently needed to meet the drug evaluation criteria. Specifically, the pharmacological and immunological profiles of RNA nanoparticles need to be systematically studied to provide insights in rational design of RNA-based therapeutics. By virtue of its programmability and biocompatibility, RNA molecules can be designed to construct sophisticated nanoparticles with versatile functions/applications and highly tunable physicochemical properties. This intrinsic characteristic allows the systemic study of the effects of various properties of RNA nanoparticles on their in vivo behaviors such as cancer targeting and immune responses. This review will focus on the recent progress of RNA nanoparticles in cancer targeting and summarize the effects of common physicochemical properties such as size and shape on the RNA nanoparticles’ biodistribution and immunostimulation profiles.