Polycatechols with Robust Efficiency in Cytosolic Peptide Delivery via Catechol-Boronate Chemistry

Abstract

Cytosolic delivery of peptides remains a challenging task because of the limited binding sites on peptides and the existence of multiple intracellular barriers. Here, we proposed the use of polycatechols with a high cell permeability to deliver peptides of different physicochemical properties using the catechol-boronate chemistry. Peptides were decorated with boronate moieties via three strategies, and the introduced boronate groups greatly increased the binding affinity of cargo peptides with polycatechols. The loading peptides could be released under the endolysosomal acidity. When the cargo peptide was modified with boronate moiety via a p-hydroxybenzylcarbamate self-immolative spacer, it could be loaded by polycatechols and released in a traceless manner triggered by reactive oxygen species. The proposed strategies greatly promote the cytosolic delivery efficiency of different peptides into various cell lines and restored their biofunctions after intracellular delivery and release. This study provides a general and robust platform for the intracellular delivery of membrane-impermeable peptides.

Reversible Assembly of Proteins and Phenolic Polymers for Intracellular Protein Delivery with Serum Stability

“…PC/B1-nfGFP nanoparticles in a serum-free medium caused obvious endosomal disruption according to the Gal8 recruitment assay (Figure d). This result is in accordance with our previous result reported for PC in cytosolic peptide delivery . However, significantly decreased endosome leakage was observed for the PC/B1-nfGFP nanoparticles in a serum-containing medium, which is probably due to the internalization of PC/B1-nfGFP nanoparticles by the macropinocytosis pathway after serum protein adsorption (Figure e).…”

“…This result is in accordance with our previous result reported for PC in cytosolic peptide delivery. 47 However, significantly decreased endosome leakage was observed for the PC/B1-nfGFP nanoparticles in a serum-containing medium, which is probably due to the internalization of PC/B1-nfGFP nanoparticles by the macropinocytosis pathway after serum protein adsorption (Figure 3e). Besides, the PC/B1-GFP nanoparticles were not colocalized with lysosomes stained by Lysotracker Red when incubated for 0.5−8 h (Figure 3f).…”

Protein Delivery to the Cytosol and Cell Nucleus via Micellar Nanocarrier-Based Nonendocytic Uptake

“…The phenylboronic acid component present at the micelle surface is used for polyphenol-based linking with protein, where the 1,2 diol group of polyphenol reacts with the phenylboronic acid group and the oxidized ketone group of polyphenol reacts with primary amine groups of protein. As shown in Scheme , we have selected green tea polyphenol EGCG as it is well studied, easily oxidizes at physiological condition, and was used earlier for similar conjugation. − …”

Fluorous Tagged Peptides for Intracellular Delivery and Biomedical Imaging

“…[25,26] To increase the enzymatic stability and membrane permeability of cargo peptides, various strategies including stapled peptides, polymer conjugates, or inorganic nanoparticles were proposed. [27][28][29][30][31][32][33][34][35] However, designing stapled peptides are involved with sophisticated synthesis, and the use of cationic polymers and inorganic nanoparticles to deliver peptides may cause material degradation and toxicity problems.…”