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Antiangiogenic and Antitumor Therapy for Retinoblastoma with Hypoxia-Inducible Factor-1α siRNA and Celastrol Co-Delivery Nanomicelles
Abstract
Retinoblastoma (RB) makes up about 3% of all childhood malignancies. Chemotherapy is commonly applied for RB treatment, while the clinical effectiveness varies significantly due to the cancer therapeutic resistances. Hypoxic tumor microenvironment, a hallmark of all tumors, is strongly associated with malignant progress and therapeutic resistances. The hypoxia mainly promotes the angiogenesis by upregulating pro-angiogenetic pathways. In this work, polymeric micelles are used as the carrier to deliver celastrol and siRNA to RB cells for achieving synergistic anti-tumor and antiangiogenesis effects. The micelle vectors have shown effective cellular internalization and release of loaded-celastrol and HIF-1 siRNA. The co-delivery system specifically and synergistically inhibits the expression of HIF-1α and VEGF in RB cells, suppresses the HIF-1α /VEGF/VEGFR signaling pathway, and impedes the proliferation, migration, and invasion of vascular endothelial cells. The polymer micellar carrier that co-delivers HIF-1α siRNA and celastrol is used for antiangiogenic and antitumor therapy of RB. Altogether, the results show that our polymeric micelle delivery system can be used to overcome barriers of drug resistance induced by angiogenesis and develop new drug/siRNA combinatory therapies.
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“This co-delivery system synergistically inhibits HIF-1α and VEGF expression in RB cells while suppressing the HIF-1α/VEGF/VEGFR signaling pathway, consequently impeding proliferation, migration, and invasion of vascular endothelial cells [180].”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [180]
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Recent Trends in anti-tumor mechanisms and molecular targets of celastrol
Zhu, Y., Meng, Y., Zhang, J., Liu, R., Shen, S., Gu, L., Wong, Y., Ma, A., Chai, X., Zhang, Y., et al. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.99592 · Cited by 41
“…and synergistically inhibited the expression of HIF-1α and VEGF in retinoblastoma cells, inhibited the HIF-1α /VEGF/VEGFR signaling pathway, ameliorated the hypoxic microenvironment of the tumors, and hindered the proliferation, migration, and invasion of vascular endothelial cells [65].”
BackgroundSelf-citationCelastrol: The new dawn in the treatment of vascular remodeling diseases
Tan, J.-L., Yi, J., Cao, X.-Y., Wang, F., Xie, S.-L., Zhou, L., Li, Q., & Dai, A. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.114177 · Cited by 31
Onugwu, A. L., Ugorji, O. L., Ufondu, C. A., Ihim, S. A., Echezona, A. C., Nwagwu, C. S., Onugwu, S. O., Uzondu, S. W., Agbo, C. P., Ogbonna, J. D., et al. (2023) · Nanoscale Advances · doi:10.1039/d3na00462g · Cited by 33
Li, Z., Liu, R., Zhang, X., Guo, Z., Geng, X., Chu, D., Cui, H., Zhang, A., Li, W., Zhu, L., et al. (2024) · Journal of Controlled Release · doi:10.1016/j.jconrel.2024.04.010 · Cited by 29
Self-citationNon-coding RNAs in Regulating Tumor Angiogenesis
Song, X., Guo, Y., Song, P., Duan, D., & Guo, W. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.751578 · Cited by 21
Metadata
- Authors
- Yang, F., Guo, Z., Shi, L., Li, Z., Zhang, J., Chai, C., & Li, J.
- Venue
- Journal of Biomedical Nanotechnology
- Publisher
- American Scientific Publishers
- Published
- 2020-10-01
- Volume
- 16
- Issue
- 10
- Pages
- 1471-1481
- ISSN
- 1550-7033 (ISSN-L)
- OpenAlex
- W3119662303
- Cited by
- 20
- References
- 0
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 3 · 2022: 4 · 2021: 3
- FWCI
- 0.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Biomedical Nanotechnology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Keywords
- retinoblastoma, hypoxia-inducible factor-1α, siRNA delivery, celastrol, polymeric micelles, anti-angiogenic therapy, cancer therapy, VEGF signaling, tumor hypoxia, drug resistance, combination therapy
- MeSH terms
- Child, Humans, Retinoblastoma, Triterpenes, Retinal Neoplasms, Angiogenesis Inhibitors, RNA, Small Interfering, Endothelial Cells, Cell Line, Tumor, Hypoxia-Inducible Factor 1, alpha Subunit, Pentacyclic Triterpenes, Tumor Microenvironment
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