Poly(glycidyl methacrylate)-based star-like polycations with rich hydrophilic hydroxyl groups can efficiently transfer miRNA into primary cardiac fibroblasts for effective applications in cardiac diseases, such as inhibition of cardiac fibrosis and hypertrophy.
Owing to the low cytotoxicity and excellent biocompatibility, polysaccharides are good candidates for the development of promising biomaterials. In this paper, a series of magnetic resonance imaging (MRI)-visible cationic polymeric nanoparticles involving liver cell-targeting polysaccharides were flexibly designed for multifunctional gene delivery systems. The pullulan-based vector (PuPGEA) consisting of one liver cell-targeting pullulan backbone and ethanolamine-functionalized poly(glycidyl methacrylate) (denoted by BUCT-PGEA) side chains with abundant hydroxyl units and secondary amine was first prepared by atom transfer radical polymerization. The resultant cationic nanoparticles (PuPGEA-GdL or PuPGEA-GdW) with MRI functions were produced accordingly by assembling PuPGEA with aminophenylboronic acid-modified Gd-DTPA (GdL) or GdW10O36(9-) (GdW) via the corresponding etherification or electrostatic interaction. The properties of the PuPGEA-GdL and PuPGEA-GdW nanoparticles including pDNA condensation ability, cytotoxicity, gene transfection, cellular uptake, and in vitro and in vivo MRI were characterized in details. Such kinds of cationic nanoparticles exhibited good performances in gene transfection in liver cells. PuPGEA-GdW demonstrated much better MRI abilities. The present design of PuPGEA-based cationic nanoparticles with the liver cell-targeting polysaccharides and MRI contrast agents would shed light on the exploration of tumor-targetable multifunctional gene delivery systems.
Hepatocellular carcinoma (HCC) is one of the most common cancers. Maternally expressed gene 3 (MEG3, one kind of long noncoding RNA [lncRNA]) can act as a tumor suppressor and regulate P53 target gene expression. However, lncRNA MEG3 demonstrates relatively low or no expression in human HCC. This study provides a promising concept to codeliver lncRNA and pDNA for cancer therapy. As proof‐of‐concept, the pcDNA‐MEG3 and pcDNA‐P53 plasmids‐condensed nanocomplexes with the liver‐targeting polycation gene vector, pullulan‐based ethanolamine‐modified poly(glycidyl methacrylate) (denoted as PuPGEA), are proposed to codeliver lncRNA and pDNA to treat HCC. Pullulan‐containing nanovectors are shown to be able to effectively mediate gene delivery in liver cells. To assess gene delivery performances of PuPGEA, a series of assays such as in vitro gene transfection, HCC cell proliferation, colony formation, migration, matrigel transwell assays, and in vivo xenograft animal models are carried out. The codelivery system with PuPGEA/(MEG3+P53) nanocomplexes demonstrates additive effects in suppressing HCC compared to PuPGEA/MEG3 or PuPGEA/P53 nanocomplexes alone. These results suggest that codelivery of lncRNA and pDNA by polycation nanovectors is a promising method to treat cancers.
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