ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Delivery of siRNA Using CXCR4-targeted Nanoparticles Modulates Tumor Microenvironment and Achieves a Potent Antitumor Response in Liver Cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed.
- A bibliometric analysis of global research trends in tumor microenvironment based nanotherapy.Discover nano · 2026Review
- Nanoscale delivery systems for hepatocellular carcinoma: Functionalization, delivery strategies, and clinical challenges.Materials today. Bio · 2026Review
- Emerging nanomedicine for liver diseases treatment.Journal of nanobiotechnology · 2025Review
- Gene Therapy Strategies for Hepatocellular Carcinoma (HCC): Current Landscape and Future Directions.Cancers · 2025Review
- Integrator Complex Subunit 6 Regulates Biological Nature of Hepatocellular Carcinoma by Modulating Epithelial-Mesenchymal Transition.Current issues in molecular biology · 2025Article
- Targeting the chemokine receptor CXCR4 for cancer therapies.Biomarker research · 2025Review
- Sorafenib-Drug Delivery Strategies in Primary Liver Cancer.Journal of functional biomaterials · 2025Review
- Nanocomposites to Overcoming Sorafenib Resistance in Hepatocellular Carcinoma Therapy.International journal of nanomedicine · 2025Review
- Lipid Nanovesicle Platforms for Hepatocellular Carcinoma Precision Medicine Therapeutics: Progress and Perspectives.Organogenesis · 2024Review
- Recent Advances in RNA Interference-Based Therapy for Hepatocellular Carcinoma: Emphasis on siRNA.Cell biochemistry and biophysics · 2024Review
- Medaka liver developed Human NAFLD-NASH transcriptional signatures in response to ancestral bisphenol A exposure.Research square · 2024Article
- Nanomaterials modulate tumor-associated macrophages for the treatment of digestive system tumors.Bioactive materials · 2024Review
- Sex-specific expression of the human NAFLD-NASH transcriptional signatures in the liver of medaka with a history of ancestral bisphenol A exposure.bioRxiv : the preprint server for biology · 2024Article
- Regorafenib combined with a PD-1 inhibitor in the second-line setting for unresectable hepatocellular carcinoma in real-world practice.Journal of gastrointestinal oncology · 2024Article
- Precision targeting in hepatocellular carcinoma: Exploring ligand-receptor mediated nanotherapy.World journal of hepatology · 2024Review
- Therapeutic Perspectives of HIV-Associated Chemokine Receptor (CCR5 and CXCR4) Antagonists in Carcinomas.International journal of molecular sciences · 2022Review
- Chemokine-Decorated Nanoparticles Target Specific Subpopulations of Primary Blood Mononuclear Leukocytes.Nanomaterials (Basel, Switzerland) · 2022Article
- Endothelial Cell Dysfunction and Nonalcoholic Fatty Liver Disease (NAFLD): A Concise Review.Cells · 2022Review
- Long noncoding RNA Smyca coactivates TGF-β/Smad and Myc pathways to drive tumor progression.Journal of hematology & oncology · 2022Article
- Dually Active Polycation/miRNA Nanoparticles for the Treatment of Fibrosis in Alcohol-Associated Liver Disease.Pharmaceutics · 2022Article
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Authors and funding
7 authors.
Funding
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Abstract
Antiangiogenic therapy has recently emerged as a highly promising therapeutic strategy for treating hepatocellular carcinoma (HCC). However, the only clinically approved systemic antiangiogenic agent for advanced HCC is sorafenib, which exerts considerable toxicity. Moreover, acquired resistance to antiangiogenic therapy often develops and restricts the therapeutic efficacy of this treatment. Hence, in this study, we develop a CXCR4-targeted lipid-based nanoparticle (NP) formulation to specifically deliver vascular endothelial growth factor (VEGF) siRNA as an antiangiogenic substance into HCC. AMD3100, a CXCR4 antagonist, is added into NPs to serve as both a targeting moiety and a sensitizer to antiangiogenic therapy. We demonstrate that AMD-modified NPs (AMD-NPs) can efficiently deliver VEGF siRNAs into HCC and downregulate VEGF expression in vitro and in vivo. Despite the upregulation of the SDF1α/CXCR4 axis upon the induction of hypoxia after antiangiogenic therapy, CXCR4 inhibition by AMD-NPs in combination with either conventional sorafenib treatment or VEGF siRNA prevents the infiltration of tumor-associated macrophages. These dual treatments also induce synergistic antiangiogenic effects and suppress local and distant tumor growth in HCC. In conclusion, the tumor-targeted multifunctional AMD-NPs that co-deliver VEGF siRNA and AMD3100 provide an effective approach for overcoming tumor evasion of antiangiogenic therapy, leading to delayed tumor progression in HCC.
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