Polymeric Carriers for Delivery of RNA Cancer Therapeutics

Abstract

As research uncovers the underpinnings of cancer biology, new targeted therapies have been developed. Many of these therapies are small molecules, such as kinase inhibitors, that target specific proteins; however, only 1% of the genome encodes for proteins and only a subset of these proteins has 'druggable' active binding sites. In recent decades, RNA therapeutics have gained popularity due to their ability to affect targets that small molecules cannot. Additionally, they can be manufactured more rapidly and cost-effectively than small molecules or recombinant proteins. RNA therapeutics can be synthesised chemically and altered quickly, which can enable a more personalised approach to cancer treatment. Even though a wide range of RNA therapeutics are being developed for various indications in the oncology setting, none has reached the clinic to date. One of the main reasons for this is attributed to the lack of safe and effective delivery systems for this type of therapeutic. This review focuses on current strategies to overcome these challenges and enable the clinical utility of these novel therapeutic agents in the cancer clinic.

Keywords: RNA cancer therapeutics; polymeric carriers.

Figure 1

(a) Chemical structures of commonly used polymers in RNA therapeutics. (b) Schematical illustrations of different polymer architectures and topologies.

Figure 2

Active and passive strategies for tissue targeting of polymeric carriers.

Figure 3

Endosomal escape. Proton sponge effect.

Figure 4

Smart polymeric nanocarriers respond to endogenous and exogenous stimuli which trigger shell detachment, endosomal escape and RNA release into the cytoplasm.