Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Li, M; Su, Y; Zhang, F; Chen, K; Xu, X; Xu, L; Zhou, J; Wang, W.
A dual-targeting reconstituted high density lipoprotein leveraging the synergy of sorafenib and antimiRNA21 for enhanced hepatocellular carcinoma therapy.
Acta Biomater. 2018; 75(10):413-426
Doi: 10.1016/j.actbio.2018.05.049
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Zhang Fangrong
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- Abstract:
- 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 antisense 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 ανβ3-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. Sorafenib (So) is a multi-target kinase inhibitor which was approved by FDA as first-line drug for hepatocellular carcinoma (HCC) therapy. However, long term application of So in clinic was hampered by serious dermal toxicity and drug resistance. Although numerous researchers were devoted to finding alternatives or therapies as combination treatments with So to reach more desired therapeutic efficacy, the therapeutic options were still limited. The present study prepares RGD pentapeptide decorated biomimic reconstituted high-density lipoprotein (rHDL) loaded with So and antimiRNA21 (RGD-rHDL/So/antimiRNA21) for enhanced HCC therapy. The RGD-rHDL/So/antimiRNA21 NPs offer an effective platform for anti-tumor and anti-angiogenesis therapy in HCC and provide new approach to reverse drug-resistance of So for feasible clinical application. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Carcinoma, Hepatocellular - drug therapy
- Carcinoma, Hepatocellular - genetics
- Carcinoma, Hepatocellular - metabolism
- Carcinoma, Hepatocellular - pathology
- Female -
- Hep G2 Cells -
- Human Umbilical Vein Endothelial Cells -
- Humans -
- Lipoproteins, HDL - chemistry
- Lipoproteins, HDL - pharmacokinetics
- Lipoproteins, HDL - pharmacology
- Liver Neoplasms - drug therapy
- Liver Neoplasms - genetics
- Liver Neoplasms - metabolism
- Liver Neoplasms - pathology
- Mice -
- Mice, Inbred BALB C -
- MicroRNAs - antagonists & inhibitors
- MicroRNAs - genetics
- MicroRNAs - metabolism
- Oligopeptides - chemistry
- Oligopeptides - pharmacokinetics
- Oligopeptides - pharmacology
- RNA, Neoplasm - antagonists & inhibitors
- RNA, Neoplasm - genetics
- RNA, Neoplasm - metabolism
- Sorafenib - chemistry
- Sorafenib - pharmacokinetics
- Sorafenib - pharmacology
- Find related publications in this database (Keywords)
- Hepatocellular carcinoma
- Reconstituted high density lipoprotein
- Sorafenib
- antimiRNA21
- Anti-angiogenesis