Academic Journal
E-selectin targeting cascaded ultrasonic cavitation enables liposomes to deeply penetrate pancreatic cancer.
| Τίτλος: | E-selectin targeting cascaded ultrasonic cavitation enables liposomes to deeply penetrate pancreatic cancer. |
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| Συγγραφείς: | Hu C; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China., Chen J; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China; Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China., Liu X; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China., Zhao Y; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China., Pan H; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China., Fang X; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China; Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China., Yin H; Department of Ultrasonic Diagnostic Center, Ningbo No. 2 Hospital, Ningbo, 315010, PR China., Wang G; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China; Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China. Electronic address: wangguowei@zju.edu.cn., Huang P; Department of Ultrasound in Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China; Research Center of Ultrasound in Medicine and Biomedical Engineering, The Second Affiliated Hospital of Zhejiang University School of Medicine, Zhejiang University, Hangzhou, 310009, PR China. Electronic address: huangpintong@zju.edu.cn. |
| Πηγή: | Cancer letters [Cancer Lett] 2026 Feb 28; Vol. 639, pp. 218129. Date of Electronic Publication: 2025 Nov 14. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE |
| Imprint Name(s): | Publication: Limerick : Elsevier Science Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
| Ιατρικοί όροι (MeSH): | Pancreatic Neoplasms*/drug therapy , Pancreatic Neoplasms*/pathology , Pancreatic Neoplasms*/metabolism , E-Selectin*/metabolism , Deoxycytidine*/analogs & derivatives , Deoxycytidine*/administration & dosage , Deoxycytidine*/pharmacology , Deoxycytidine*/pharmacokinetics , Deoxycytidine*/chemistry , Drug Delivery Systems*/methods , Liposomes*, Fluorocarbons/chemistry ; Fluorocarbons/administration & dosage ; Prodrugs/administration & dosage ; Humans ; Animals ; Gemcitabine ; Cell Line, Tumor ; Mice ; Xenograft Model Antitumor Assays ; Pentanes |
| Περίληψη: | The insufficient vascular extravasation and dense extracellular matrix in pancreatic cancer jointly resist drug accumulation and penetration into tumor and lead to poor prognosis. The ligand/receptor-mediated nanocarrier has gained widespread recognition as an effective strategy for increasing the tumor targeting accumulation, but which is always impaired by protein corona pollution during circulation, as well as limited intratumor penetration. To address these problems, we have designed an E-selectin targeting cascaded ultrasonic cavitation liposome (GPGLP) that incorporates a gemcitabine prodrug (GOE), perfluoropentane, and an endogenous ligand ganglioside (GM1), which can sequentially overcome the biological barriers of tumor endothelial cells and the extracellular matrix via ligand/receptor-mediated transcytosis and ultrasonic cavitation-induced extracellular matrix loosening. The endogenous GM1 ganglioside can reduce the protein corona formation of liposome and guarantee its capability to recognize the E-selectin receptor on tumor neovascularization, initiating ligand/receptor-mediated transcytosis for efficient tumor accumulation. Upon exposure to ultrasound irradiation, GPGLP liposomes undergo a liquid-to-gas phase transition and self-assemble into smaller liposomes. The in-situ cavitation force following facilitates the extracellular matrix loosening, augmenting GPGLP deep penetration within the tumor parenchyma and releasing active gemcitabine throughout the tumor after intracellular enzymolysis. This process results in potent antitumor efficacy superior to that of clinical chemotherapeutics in pancreatic cancer treatement. This study presents an effective strategy of transcytosis cascaded ultrasonic cavitation to tackle the biological barriers in drug delivery for pancreatic cancer and other solid tumors. (Copyright © 2025. Published by Elsevier B.V.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: E-selectin; Liposome; Pancreatic cancer; Transcytosis; Ultrasound cavitation |
| Substance Nomenclature: | 0 (Liposomes) 0 (E-Selectin) 0 (Gemcitabine) 0W860991D6 (Deoxycytidine) 678-26-2 (perfluoropentane) 0 (Fluorocarbons) 0 (Prodrugs) 0 (Pentanes) |
| Entry Date(s): | Date Created: 20251116 Date Completed: 20260122 Latest Revision: 20260127 |
| Update Code: | 20260130 |
| DOI: | 10.1016/j.canlet.2025.218129 |
| PMID: | 41242489 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1872-7980 |
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| DOI: | 10.1016/j.canlet.2025.218129 |