<i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer
The urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic <i>N</i>-alkylisatin (<i>N</i>-AI)-loaded liposomes functionalized with the uPA/uPAR targeting ligand, plasmino...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/12/7/641 |
| _version_ | 1797563113359278080 |
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| author | Lisa Belfiore Darren N. Saunders Marie Ranson Kara L. Vine |
| author_facet | Lisa Belfiore Darren N. Saunders Marie Ranson Kara L. Vine |
| author_sort | Lisa Belfiore |
| collection | DOAJ |
| description | The urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic <i>N</i>-alkylisatin (<i>N</i>-AI)-loaded liposomes functionalized with the uPA/uPAR targeting ligand, plasminogen activator inhibitor type 2 (PAI-2/SerpinB2), and assessed liposome uptake in vitro and in vivo. Receptor-dependent uptake of PAI-2-functionalized liposomes was significantly higher in the uPA/uPAR overexpressing MDA-MB-231 breast cancer cell line relative to the low uPAR/uPAR expressing MCF-7 breast cancer cell line. Furthermore, <i>N</i>-AI cytotoxicity was enhanced in a receptor-dependent manner. In vivo, PAI-2 <i>N</i>-AI liposomes had a plasma half-life of 5.82 h and showed an increased accumulation at the primary tumor site in an orthotopic MDA-MB-231 BALB/c-Fox1nu/Ausb xenograft mouse model, relative to the non-functionalized liposomes, up to 6 h post-injection. These findings support the further development of <i>N</i>-AI-loaded PAI-2-functionalized liposomes for uPA/uPAR-positive breast cancer, especially against triple-negative breast cancer, for which the prognosis is poor and treatment is limited. |
| first_indexed | 2024-03-10T18:37:58Z |
| format | Article |
| id | doaj.art-e0e22e6ec93d4b77a111d520206598d6 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-10T18:37:58Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-e0e22e6ec93d4b77a111d520206598d62023-11-20T06:04:59ZengMDPI AGPharmaceutics1999-49232020-07-0112764110.3390/pharmaceutics12070641<i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast CancerLisa Belfiore0Darren N. Saunders1Marie Ranson2Kara L. Vine3Illawarra Health and Medical Research Institute, Wollongong, NSW 2522, AustraliaSchool of Medical Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaIllawarra Health and Medical Research Institute, Wollongong, NSW 2522, AustraliaIllawarra Health and Medical Research Institute, Wollongong, NSW 2522, AustraliaThe urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic <i>N</i>-alkylisatin (<i>N</i>-AI)-loaded liposomes functionalized with the uPA/uPAR targeting ligand, plasminogen activator inhibitor type 2 (PAI-2/SerpinB2), and assessed liposome uptake in vitro and in vivo. Receptor-dependent uptake of PAI-2-functionalized liposomes was significantly higher in the uPA/uPAR overexpressing MDA-MB-231 breast cancer cell line relative to the low uPAR/uPAR expressing MCF-7 breast cancer cell line. Furthermore, <i>N</i>-AI cytotoxicity was enhanced in a receptor-dependent manner. In vivo, PAI-2 <i>N</i>-AI liposomes had a plasma half-life of 5.82 h and showed an increased accumulation at the primary tumor site in an orthotopic MDA-MB-231 BALB/c-Fox1nu/Ausb xenograft mouse model, relative to the non-functionalized liposomes, up to 6 h post-injection. These findings support the further development of <i>N</i>-AI-loaded PAI-2-functionalized liposomes for uPA/uPAR-positive breast cancer, especially against triple-negative breast cancer, for which the prognosis is poor and treatment is limited.https://www.mdpi.com/1999-4923/12/7/641<i>N</i>-alkylisatinliposomeurokinase plasminogen activatorPAI-2SerpinB2breast cancer |
| spellingShingle | Lisa Belfiore Darren N. Saunders Marie Ranson Kara L. Vine <i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer Pharmaceutics <i>N</i>-alkylisatin liposome urokinase plasminogen activator PAI-2 SerpinB2 breast cancer |
| title | <i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer |
| title_full | <i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer |
| title_fullStr | <i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer |
| title_full_unstemmed | <i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer |
| title_short | <i>N</i>-Alkylisatin-Loaded Liposomes Target the Urokinase Plasminogen Activator System in Breast Cancer |
| title_sort | i n i alkylisatin loaded liposomes target the urokinase plasminogen activator system in breast cancer |
| topic | <i>N</i>-alkylisatin liposome urokinase plasminogen activator PAI-2 SerpinB2 breast cancer |
| url | https://www.mdpi.com/1999-4923/12/7/641 |
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