Micelle-like nanoparticles as carriers for DNA and siRNA

Abstract

Gene therapy represents a potential efficient approach of disease prevention and therapy. However, due to their poor in vivo stability, gene molecules need to be associated with delivery systems to overcome extracellular and intracellular barriers and allow access to the site of action. Cationic polymeric nanoparticles are popular carriers for small interfering RNA (siRNA) and DNA-based therapeutics for which efficient and safe delivery are important factors that need to be optimized. Micelle-like nanoparticles (MNP) (half micelles, half polymeric nanoparticles) can overcome some of the disadvantages of such cationic carriers by unifying in one single carrier the best of both delivery systems. In this review, we will discuss how the unique properties of MNP including self-assembly, condensation and protection of nucleic acids, improved cell association and gene transfection, and low toxicity may contribute to the successful application of siRNA- and DNA-based therapeutics into the clinic. Recent developments of MNP involving the addition of stimulus-sensitive functions to respond specifically to pathological or externally applied "triggers" (e.g., temperature, pH or enzymatic catalysis, light, or magnetic fields) will be discussed. Finally, we will overview the use of MNP as two-in-one carriers for the simultaneous delivery of different agents (small molecules, imaging agents) and nucleic acid combinations.

Keywords: DNA delivery; cationic amphiphiles; cationic polymers; complexes; gene delivery; micelle-like nanoparticles; siRNA delivery.

Figure 1

Schematic explanation of the main hurdles in siRNA/pDNA delivery using cationic carriers from the administration site to the target site.

Figure 2

Micelle-like nanoparticles for gene delivery are constructed from amphiphilic diblock AB or triblock ABC copolymers where A counts for the hydrophobic micelle-forming segment, B for the cationic nucleic acid-loading segment, and C for hydrophilic micelle-stabilizer segment.