Boronic acid-rich dendrimer for efficient intracellular peptide delivery

Abstract

Interests in intracellular peptide delivery have continued to grow, significantly fueled by the importance of peptides and their mimetics in modern cell biology and pharmaceutical industry. However, efficient intracellular delivery of membrane-impermeable peptides of different polarities remains a challenging task. In this study, we develop a general and robust strategy for intracellular peptide delivery by using a boronic acid-rich dendrimer. The designed material is capable of transporting peptides with different polarities and charge properties into the cytosol of various cell lines without inducing additional cytotoxicity. The transduction efficacy and proteolytic stability of cargo peptides delivered by the boronic acid-rich dendrimer are much superior to peptides conjugated with cell penetrant peptides such as octaarginine. In addition, the bioactivities of pro-apoptotic peptides are maintained after intracellular delivery. This study provides a versatile and robust platform for the intracellular delivery of membrane-impermeable peptides.

Aminoglycoside‐Based Biomaterials: From Material Design to Antibacterial and Gene Delivery Applications

“…Hyperbranched polymers have been widely used as carriers in gene and protein delivery due to their higher charge density, which may be beneficial for biomolecule binding. [ 132–138 ] Despite the effectiveness of hyperbranched polycations in gene transfection, there still exists a contradictory correlation between the transfection efficiency and polymer cytotoxicity, where the high molecular weight polymers usually exhibit a high transfection efficiency but with high toxicity, [ 136 ] while the low molecular weight ones with low cytotoxicity usually possess poor transfection efficiency. [ 139–141 ] One possible solution to solve this paradox is to use low molecular weight polycations to construct biodegradable polymers.…”

Strategies in the delivery of Cas9 ribonucleoprotein for CRISPR/Cas9 genome editing

“…To ensure efficient RNP binding to the dendrimer scaffold, the polymer was functionalized with a high density of phenylboronic acid (PBA) moieties on the surface 57 . PBA is an electron-deficient group that is capable of binding amine and imidazole groups on proteins via nitrogen-boronate complexation 207 , 208 . The residual amine groups on a generation 5 (G5) polyamidoamine (PAMAM) dendrimer could bind with anionic groups on proteins via electrostatic interactions.…”

Design of Polymers for Intracellular Protein and Peptide Delivery

“…Besides proteins, the polymer also successfully delivered peptides of different hydrophobicity and isoelectric points into living cells, maintaining their bioactivity. [ 17 ] These boronate polymers could be also used in combination with natural polyphenols in cytosolic protein delivery. [ 18 ] Natural polyphenols such as (−)‐epigallocatechin‐3‐O‐gallate (EGCG) could interact with biomolecules such as proteins and nucleic acids via a combination of hydrogen bonding and hydrophobic interactions, [ 19 ] and this property allows them to co‐assemble with these biomolecules, yielding nanoparticles bearing polyphenol moieties.…”