期刊
BIOMATERIALS
卷 104, 期 -, 页码 192-200出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2016.07.016
关键词
miRNA therapy; Delivery system; Hepatocellular carcinoma; Multifunctional delivery
资金
- National Natural Science Foundation of China [81502026, 21374098, 81530079]
- Zhejiang Provincial Natural Science Foundation [LQ16H180002]
- Zhejiang Provincial Key Innovative Team [2013TD06]
Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supra molecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment. (C) 2016 Elsevier Ltd. All rights reserved.
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