PGMA-based gene carriers with lipid molecules

Abstract

Lipids, as the greatest constituent in cell membranes, have been widely used for biomedical applications because of their excellent biological properties. The introduction of membrane lipid molecules into gene vectors would embody greater biocompatibility, cellular uptake and transfection efficiency. In this work, one flexible strategy for readily conjugating lipid molecules with polycations was proposed based on atom transfer radical polymerization to produce a series of cholesterol (CHO)- and phosphatidylinositol (PI)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s, namely CHO-PGEAs and PI-PGEAs, as effective gene carriers. CHO-PGEAs and PI-PGEAs truly demonstrated much better transfection performances compared to linear ethanolamine-functionalized poly(glycidyl methacrylate) (denoted as BUCT-PGEA) counterparts and traditional standard branched polythylenimine (PEI, 25 kDa). In addition, the good antitumor effects of CHO-PGEA and PI-PGEA were confirmed with suppressor tumor gene p53 systems in vitro and in vivo. The present work could provide a new strategy to develop effective cationic conjugation of lipid molecules for gene therapy.

CRISPR/Cas9 Delivery Mediated with Hydroxyl‐Rich Nanosystems for Gene Editing in Aorta

“…[30] Polycation to pDNA ratios are expressed as molar ratios of nitrogen (N) in polymer to phosphate (P) in pDNA (or as N/P ratios). [30] Polycation to pDNA ratios are expressed as molar ratios of nitrogen (N) in polymer to phosphate (P) in pDNA (or as N/P ratios).…”

“…Sci. [30] Then, we evaluated the potential of CHO-PGEA for the delivery of plasmid-based CRISPR/Cas9 system. a) Schematic diagram of pCas9-sgFbn1 plasmid.…”

“…Figure S6 in the Supporting Information showed that the cytotoxicity was increased with the increase of N/P ratio. [30] Considering both Cas9 plasmid transfection and cytotoxicity, the optimal ratio N/P of 15 was used to detect the potential of CHO-PGEA to deliver CRISPR/Cas9 system at the following experiments. [30] Considering both Cas9 plasmid transfection and cytotoxicity, the optimal ratio N/P of 15 was used to detect the potential of CHO-PGEA to deliver CRISPR/Cas9 system at the following experiments.…”

“…[31] The cellular uptake efficiency of nanoparticles was assessed by delivering YOYO-1-labeled Cas9-sgFbn1 plasmid in VSMCs. [30] Effective endosome escape is a key characteristic for nanoparticle-mediated gene expression. The higher ability of CHO-PGEA/pCas9-sgFbn1 nanoparticles to overcome cellular membranes barriers could be explained by the introduction of CHO, which might readily change membrane fluidity and increase biocompatibility.…”

“…[24][25][26] Such hydroxylrich gene vector has great potential for the treatment of heart disease and tumors. [30] Moreover, lipid-based carriers can effectively enhance the transfection efficiency because lipids are the important components of cell membranes. [30] Moreover, lipid-based carriers can effectively enhance the transfection efficiency because lipids are the important components of cell membranes.…”