Bio-Inspired Supramolecular Hybrid Dendrimers Self-Assembled from Low-Generation Peptide Dendrons for Highly Efficient Gene Delivery and Biological Tracking

Currently, supramolecular self-assembly of dendrons and dendrimers emerges as a powerful and challenging strategy for developing sophisticated nanostructures with excellent performances. Here we report a supramolecular hybrid strategy to fabricate a bio-inspired dendritic system as a versatile delivery nanoplatform. With a rational design, dual-functionalized low-generation peptide dendrons (PDs) self-assemble onto inorganic nanoparticles via coordination interactions to generate multifunctional supramolecular hybrid dendrimers (SHDs). These SHDs exhibit well-defined nanostructure, arginine-rich peptide corona, and fluorescent signaling properties. As expected, our bio-inspired supramolecular hybrid strategy largely enhances the gene transfection efficiency of SHDs approximately 50 000-fold as compared to single PDs at the same RIP ratio. Meanwhile the bio-inspired SHDs also (i) provide low cytotoxicity and serum resistance in gene delivery; (ii) provide inherent fluorescence for tracking intracellular pathways including cellular uptake, endosomal escape, and gene release; and (iii) work as an alternative reference for monitoring desired protein expression. More importantly, in vivo animal experiments demonstrate that SHDs offer considerable gene transfection efficiency (in muscular tissue and in HepG2 tumor xenografts) and real-time bioimaging capabilities. These SHDs will likely stimulate studies on bio-inspired supramolecular hybrid dendritic systems for biomedical applications both in vitro and in vivo.