Fluoroalkylation promotes cytosolic peptide delivery

Abstract

Cytosolic delivery of peptides remains a challenging task owing to their susceptibility to enzymatic degradation and the existence of multiple intracellular barriers. Here, we report a new strategy to address these issues by decoration of a fluorous tag on the terminal of cargo peptides. The fluorous-tagged peptides were assembled into nanostructures, efficiently internalized by cells via several endocytic pathways and released into the cytosol after endosomal escape. They were relatively stable against enzymatic degradation and showed much higher efficiency than nonfluorinated analogs and cell penetrant peptide–conjugated ones. The proposed strategy also efficiently delivered a proapoptotic peptide into specific sites in the cells and restored the function of cargo peptide after cytosolic delivery. The fluorous-tagged proapoptotic peptide efficiently inhibited tumor growth in vivo. This study provides an efficient fluorination strategy to promote the cytosolic delivery of peptides.

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

“…Peptides can be decorated with lipid moieties to yield a class of lipopeptides with self-assembly behaviors and increased membrane permeability 185 - 187 . For example, a helical amphiphilic peptide consisting of arginine, leucine and two reactive hydrazide moieties was used as the scaffold to design lipopeptides 188 .…”

Fluoropolymer‐Mediated Intracellular Delivery of miR‐23b for the Osteocyte Differentiation in Osteoblasts

“…[29] Other than these methods, fluorination is a widely accepted method that significantly improves the transfection efficacy of DNA, siRNA, miRNA, proteins, and peptides owing to the presence of a unique fluorine effect during transfection. [20,[30][31][32][33][34] In this study, heptafluorobutyric anhydride was used to modify the dendrimer PAMAM to synthesize a derivative fluoropolymer (FP), which was then used for miR-23b delivery to examine the efficacy of regulation of osteogenic differentiation Emerging evidence suggests that microRNAs (miRNAs) play key roles in the regulation of multiple biological processes, including the differentiation of osteoblasts. Although miRNA-based gene therapy holds immense potential in the treatment of a variety of diseases, the intracellular delivery of miRNA remains challenging owing to the lack of efficient and safe gene carriers.…”

“…Notably, FP/miR-23b nanoparticles exhibited a higher transfection efficiency compared to PAMAM/miR-23b that was attributed to the unique fluorine effect during gene transfection. [20,[30][31][32][33][34] Further, the intracellular distribution of FP/ miR-23b nanoparticles was investigated using confocal laser scanning microscopy (CLSM) to test their capability of endosomal escape, which is important for execution of the miR-23b functions in the cytosol (Figure 2). Clear, co-location pattern of green and red fluorescence was observed after miR-23b transfection for 3 and 6 h, indicating that the FP/miR-23b nanoparticles were internalized by the cells and trapped in the lysosomes.…”

“…[ 29 ] Other than these methods, fluorination is a widely accepted method that significantly improves the transfection efficacy of DNA, siRNA, miRNA, proteins, and peptides owing to the presence of a unique fluorine effect during transfection. [ 20,30–34 ]…”

Nanovesicle-Mediated Delivery Systems for CRISPR/Cas Genome Editing

“…Applied to polymer chemistry, fluorination can affect interactions of modified polymers with cellular membranes. Fluorinated materials have been reported to increase the binding affinity for cell membranes and promote endosome escape [ 72 ]. In addition, fluorinated polymers feature an extreme low surface energy, which assists polymer aggregation even at low concentrations [ 73 ].…”