Journal
ACTA BIOMATERIALIA
Volume 75, Issue -, Pages 413-426Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2018.05.049
Keywords
Hepatocellular carcinoma; Reconstituted high density lipoprotein; Sorafenib; antimiRNA21; Anti-angiogenesis
Funding
- National Natural Science Foundation of China [81502680, 81102398]
- National Major Scientific and Technological Special Project for Significant New Drugs Development [2016ZX09101031]
- Graduate Cultivation Innovative Project of Jiangsu Province [SJLX16_0239]
- National Foundation for Fostering Talents of Basic Science [J1030830]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
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Sorafenib (So) is a multi-target kinase inhibitor extensively used in clinic for hepatocellular carcinoma therapy. It demonstrated strong inhibition both in tumor proliferation and tumor angiogenesis, while hampered by associated cutaneous side-effect and drug resistance. The knockdown of miR-21 with anti sense oligonucleotides (antimiRNA21) was regarded as an efficient strategy for increasing tumor sensibility to chemotherapy, which could be employed to appreciate the efficacy of So. Herein, we successfully formulated a dual-targeting delivery system for enhanced hepatocellular carcinoma therapy by encapsulating So and antimiRNA21 in RGD pentapeptide-modified reconstituted high-density lipoprotein (RGD-rHDL/So/antimiRNA21). The RGD and apolipoprotein A-I (ApoA-I) on nanoparticles (NPs) could drive the system simultaneously to tumor neovascular and parenchyma by binding to the overexpressed alpha nu beta 3-integrin and SR-B1 receptors, achieving precise delivery of therapeutics to maximize the efficacy. A series in vitro and in vivo experiments revealed that co-delivery of So and antimiRNA21 by RGD-rHDL significantly strengthened the anti-tumor and anti-angiogenic effect of So with negligible toxicity towards major organs, reversed drug-resistance and was capable of remodeling tumor environments. The constructed RGD-rHDL/So/antimiRNA21 with improved efficacy and excellent tumor targeting ability provided new idea for chemo-gene combined therapy in hepatocellular carcinoma. (C) 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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