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Effective Therapy Using a Liposomal siRNA that Targets the Tumor Vasculature in a Model Murine Breast Cancer with Lung Metastasis
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Title: | Effective Therapy Using a Liposomal siRNA that Targets the Tumor Vasculature in a Model Murine Breast Cancer with Lung Metastasis |
Authors: | Sakurai, Yu Browse this author | Hada, Tomoya Browse this author | Kato, Akari Browse this author | Hagino, Yuta Browse this author | Mizumura, Wataru Browse this author | Harashima, Hideyoshi Browse this author →KAKEN DB |
Issue Date: | 21-Dec-2018 |
Publisher: | Cell Press |
Journal Title: | Molecular therapy oncolytics |
Volume: | 11 |
Start Page: | 102 |
End Page: | 108 |
Publisher DOI: | 10.1016/j.omto.2018.10.004 |
Abstract: | Although metastatic cancer is a major cause of death for cancer patients, no efficacious treatment for metastasis is available. We previously showed that the growth of a primary tumor could be inhibited by the administration of an antiangiogenic small interfering RNA (siRNA) that is encapsulated in an RGD peptide-modified lipid nanoparticle (RGD-LNP). We herein report on the delivery of siRNA by an RGD-LNP to the vasculature is also effective for treating metastatic tumors. We compared the RGD-LNP with the polyethylene glycol (PEG)ylated LNP (PEG-LNP) in terms of accumulation in a lung-metastasized model. Despite malformed structure of vasculature in the metastasized lung, the accumulation of the PEG-LNP in the metastasized lung was lower than that for the RGD-LNP, which suggests that the delivery strategy based on vascular permeability is not completely effective for targeting metastasis tumors. The systemic injection of the RGD-LNP induced a significant silencing in the metastasized vasculature, but not in the normal lung. In addition, the continuous injection of the RGD-LNP encapsulating siRNA against a delta-like ligand 4 (DLL4) drastically prolonged the overall survival of metastasized model mice. Accordingly, our current findings suggest that vasculature targeting would be more effective than enhanced permeability and retention effect-based therapy for the treatment of metastatic cancer. |
Rights: | https://creativecommons.org/licenses/by/4.0/ |
Type: | article |
URI: | http://hdl.handle.net/2115/72409 |
Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 原島 秀吉
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