Tuning the size, shape and structure of RNA nanoparticles for favorable cancer targeting and immunostimulation

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. After the first milestone of small molecule drugs and the second milestone of antibody drugs, it was predicted that RNA drugs, either RNA itself or chemicals/ligands that target RNA, will be the third milestone in drug development. 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. This article is categorized under: Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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“…Natural materials include chitosan, starch, alginate, cellulose, β-glucan yeast ghost particles or biosynthesized poly β-hydroxybutyrate. Synthetic materials include polyurethane, polylactic acid, poly (lactic-co-glycolic acid) (PLGA) and polymethyl methacrylate resins [ 60 , 174 , 175 , 176 , 177 , 178 ]. Especially natural materials have been extensively investigated for oral vaccine delivery due to their high biodegradability and compatibility, low to non-existing toxicity, strong adjuvanticity effects and their ability to retain the conformational structure of their loaded antigen [ 59 ].…”