Bioactive clusters promoting cell penetration and nucleic acid complexation for drug and gene delivery applications: from designed to self-assembled and responsive systems

Bioactive low-molecular-weight compounds are actively pursued, as an alternative to macromolecules, for biomedical applications such as drug and gene delivery. However, achieving effective biomolecular surface recognition with small molecules is a considerable challenge. We review herein recent progresses that have been made in the identification of bioactive cationic clusters that promote cell penetration and nucleic acid complexation and vectorisation. We further emphasize the emerging use of self-assembly processes, based on supramolecular interactions and/or dynamic covalent chemistry, for generating bioactive cationic clusters. Interestingly, the introduction of molecular and/or supramolecular dynamics endows reversibility to the multivalent recognition processes, thereby paving the way toward the development of "smart'' adaptive and responsive devices that emulate the behaviour of natural systems for the dynamic control of bioactivity.