Smart micelleplexes as a new therapeutic approach for RNA delivery

ABSTRACT

Introduction: Recent scientific discoveries have revealed the potential of using RNA molecules as therapeutic agents/targets. However, a significant key factor in the success of RNA-based therapeutics is the development of vehicles that allow their efficient delivery in the correct dose, time and location, without causing unwanted side effects.

Areas covered: In this review, we provide an overview of the recent approaches proposed to overcome the chemical, biochemical and physiological barriers still present in the delivery of RNA-based therapeutics, in addition we will be discuss their use and drawbacks. This review highlights current knowledge and progress in the field of delivery of these therapeutic oligoribonucleotides, namely the use of micelleplexes as highly promising carriers. Finally, it is presented an analysis in what concerns to the ongoing challenges and future directions that have to be addressed to ensure the specificity and efficacy of RNA-based therapeutics for clinical application.

Expert opinion: Micelleplexes can be prepared with different morphologies and stability depending on the block copolymer composition and structure. Besides, micelleplex functionalization with active targeting ligands and/or polymers allows RNA delivery or co-delivery (with chemotherapeutics agents) in a single nanocarrier, improving their therapeutic efficacy, selectivity and RNA release.

KEYWORDS:

• Polymeric micelles
• gene therapy
• RNAs-based therapeutics agents
• targeted delivery

Article highlights

• RNA emerged as one of the major classes of therapeutic molecules, acting as therapeutic agents or targets.

• Extra and intracellular barriers dramatically affect the delivery of RNA-based drugs, limiting the success of RNA clinical application.

• Polymer micelles represent a powerful and versatile nanotherapeutic platform for the delivery of RNA-based drugs.

• Polymer micelles can be synthesized with defined size and superficial charge, structure and conformation, depending on the amphiphilic copolymers architecture, the solution parameters and the nature and strength of core-drug interactions to encapsulate and protect RNA molecules.

• Many types of copolymers have been used for micelle formation that can be easily functionalized to improve RNA-based drugs pharmacokinetics.

• Polymeric micelles show important features that can contribute to the successful application of RNA-based therapeutics into the clinic, including self-assembly, micellization capacity, biocompatibility, thermodynamic stability, large exclusion volume, effective condensation and protection of RNA, low toxicity, ability to bind biological membranes (enhance cell interaction and gene transfection) and improve intracellular trafficking via endosomal escape mechanism.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This work was financially supported by Fundação para a Ciência e a Tecnologia of Portugal (UID/QUI/50006/2013 and PTDC/CTM-BIO/1518/2014) and FEDER, under the Partnership Agreement PT2020.