Supramolecular dendrimer-containing layer-by-layer nanoassemblies for bioapplications: current status and future prospects

Dendrimers are powerful synthetic macromolecular architectures for a wide variety of bioapplications owing to their unique and superior features, including monodispersity, well-defined and highly branched architecture, multivalency, tunable size and shape, good water solubility, bioavailability, and precisely controllable size at the nanometer-scale. However, the cationic and higher generation dendrimers have generally proven to raise cytotoxicity concerns, which leads to the disruption of cell membranes and cell death, thus extensively limiting their use. Hence, the chemical functionalization of dendrimers’ surface with desired functional moieties and their incorporation within supramolecular Layer-by-Layer (LbL) assemblies has been reported as an effective strategy to circumvent the safety issues and improve their biological performance. Herein, we systematically review the multitude of intermolecular interactions behind the build-up of supramolecular dendrimer-containing multifunctional LbL nanoensembles with improved properties and enhanced functionalities for being used in a wide variety of bioapplications. We envisage that such diversity of intermolecular interactions may increase the number of building blocks that can be combined with dendrimers and processed into robust supramolecular multifunctional nanoarchitectures across multiple length scales well-suited to be applied in biological and biomedical scenarios, including in controlled drug/therapeutics/nucleic acid delivery, gene therapy, biosensing, bioimaging, and tissue engineering and regenerative medicine. The review also provides a glimpse on the integration of the bottom-up LbL assembly technology with other bottom-up or top-down approaches for shaping increasingly complex and sophisticated dendrimer-based supramolecular multifunctional devices with high capability for being translated into practical bioapplications.