Effective Codelivery of lncRNA and pDNA by Pullulan‐Based Nanovectors for Promising Therapy of Hepatocellular Carcinoma |
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| Authors: | Yanli Ren Rui‐Quan Li Yi‐Ran Cai Tian Xia Ming Yang Fu‐Jian Xu |
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| Affiliation: | 1. Beijing Advanced Innovation Center for Soft Matter Science and Engineering, State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, China;2. Department of Pathology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China;3. Division of Nanomedicine, Department of Medicine, University of California Los Angeles, Los Angeles, CA, USA;4. Shandong Provincial Key Laboratory of Radiation Oncology, Cancer Research Center, Shandong Cancer Hospital affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong, China |
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| Abstract: | 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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| Keywords: | gene therapy hepatocellular carcinoma long noncoding RNA nanocomplexes |
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