Clustering Small Dendrimers into Nanoaggregates for Efficient DNA and siRNA Delivery with Minimal Toxicity

Abstract

Cationic dendrimers are widely used as nonviral gene vectors, however, current gene materials based on dendrimers are either little effective or too toxic on the transfected cells. Here, a facile strategy is presented to prepare high efficient dendrimers with low transfection toxicity. Small dendrimers with 2 nm are clustered into nanoaggregates (≈100 nm) via phenylboronic acid modification and the self-assembled materials enable efficient DNA and siRNA delivery on several cell lines. The clustered nanostructures can disassemble into small dendrimers in acidic conditions thus exerting significantly less toxicity on the transfected cells. Further structure-function relationship studies reveal that both the phenyl group and boronic acid group play essential roles in the self-assembly and gene delivery processes. The transfection efficacy of phenylboronic acid-modified dendrimers can be down-regulated by blocking the boronic acid groups on dendrimers with diols or degrading the groups with hydrogen peroxide. This study provides a facile strategy in the development of efficient and biocompatible gene vectors based on low molecular weight polymers and clearly demonstrates the structure-function relationship of phenylboronic acid-modified polymers in gene delivery.

Amphiphilic carbosilane dendrons as a novel synthetic platform toward micelle formation

“…Recently, the formation of nano-sized dendrimer aggregates has been shown to increase the efficiency of nucleic acid delivery. 47 This is in agreement with the data on the comparison of the behaviour of the hexanoic and palmitic acid-bearing carbosilane dendrons presented here and support the above mentioned assumption. Thus, the organization of dendritic molecules into soft nanoparticles was essential for efficient nucleic acid binding.…”

A boronic acid–rich dendrimer with robust and unprecedented efficiency for cytosolic protein delivery and CRISPR-Cas9 gene editing

“…1). Besides the beneficial effect on protein binding, PBA moieties on polymer also provide opportunities for self-assembly and addressing the barriers existing in the cytosolic delivery of nucleic acids ( 37 , 38 ). In this study, we proposed that the PBA-rich cationic polymer is a possible candidate to bind various proteins into stable nanoparticles and allow efficient cytosolic delivery.…”

Injectable Supramolecular Hydrogels as Delivery Agents of Bcl‐2 Conversion Gene for the Effective Shrinkage of Therapeutic Resistance Tumors

“…[3a] However, despite this enormous therapeutic potential, effective gene therapy required an efficient delivery system to achieve satisfactory gene transfection efficiency for a sufficient period of time . Due to the immunology concerns of virus based gene carrier, a number of investigators have concentrated on the constructions of nonviral gene delivery systems . In the case of these cationic nonviral gene carriers, cationic polymers or polycations could interact with anionic genes by simply mixing to form polyplex, which was a nanocomplex to protect encapsulated genes and facilitate cellular uptake .…”