Fabrication of Low-Generation Dendrimers into Nanostructures for Efficient and Nontoxic Gene Delivery

Dendrimers with well-defined molecular structure and high monodispersity have gained tremendous interest in gene delivery. However, current gene carriers based on dendrimers are either not effective or are too toxic on the transfected cells. The efficacy and cytotoxicity of dendrimers are strongly correlated with their molecular weight or generation. High-generation dendrimers are reported with relatively high transfection efficacy but serious cytotoxicity due to the excess positive charges on the polymers, while low-generation dendrimers with minimal toxicity have poor polyplex stability and thus weak transfection efficacy. To break up the correlation between efficacy and toxicity, low-generation dendrimers were fabricated into various nanostructures by several strategies to improve their gene-binding capacity, polyplex stability, and transfection efficacy without inducing additional toxicity. In this review article, we will highlight recent advances in the development of assembled dendrimer nanostructures for efficient and non-toxic gene delivery. Specifically, the principles and strategies in the fabrication of dendrimer nanostructures are intensively reviewed.