Molecular nanoparticle-based gene delivery systems

The last years have witnessed an impressive development of material sciences following the burst of nanotechnology, which has greatly contributed to the development of nonviral gene delivery systems with improved properties for the efficient transport of nucleic acid payloads for gene therapy purposes. In spite of intense efforts, emulating the transfecting capabilities of viruses with synthetic systems represents an extraordinary challenge still far from accomplishment. Achieving this goal requires general and flexible approaches allowing the construction of appropriate carriers and the elucidation of the key rules governing their capacity to supramolecularly interact with nucleic acids and mediate its active transport/delivery through biological membranes. Molecular nano-objects exhibiting persistent shape- and volume, termed “molecular nanoparticles (MNPs)”, in combination with diversity-oriented precise macromolecular chemistry, offers excellent opportunities towards these goals by enabling the preorganization of functional elements, the generation of libraries of discrete architectures and the implementation of structure/activity relationship studies. The body of work on cyclodextrin, calixarene, pillarene, fullerene, macrocyclic peptide and cyclotrehalan platforms here reviewed illustrates the potential of the MNP concept to produce single isomer constructs that can be programmed to mediate the safe delivery of nucleic acids to the target cells.This study was supported by the Spanish Ministerio de Economía y Competitividad (contract numbers SAF2016-76083-R and CTQ2015-64425-C2-1-R), the Junta de Andalucía (contract number FQM2012-1467) and the European Regional Development Funds (FEDER and FSE)