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N-alkylisatin-loaded liposomes target the urokinase plasminogen activator system in breast cancer

Journal Article


Abstract


  • The urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic N-alkylisatin (N-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, N-AI cytotoxicity was enhanced in a receptor-dependent manner. In vivo, PAI-2 N-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 N-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.

Publication Date


  • 2020

Citation


  • Belfiore, L., Saunders, D. N., Ranson, M., & Vine, K. L. (2020). N-alkylisatin-loaded liposomes target the urokinase plasminogen activator system in breast cancer. Pharmaceutics, 12(7), 1-16. doi:10.3390/pharmaceutics12070641

Scopus Eid


  • 2-s2.0-85090731832

Start Page


  • 1

End Page


  • 16

Volume


  • 12

Issue


  • 7

Abstract


  • The urokinase plasminogen activator and its receptor (uPA/uPAR) are biomarkers for metastasis, especially in triple-negative breast cancer. We prepared anti-mitotic N-alkylisatin (N-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, N-AI cytotoxicity was enhanced in a receptor-dependent manner. In vivo, PAI-2 N-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 N-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.

Publication Date


  • 2020

Citation


  • Belfiore, L., Saunders, D. N., Ranson, M., & Vine, K. L. (2020). N-alkylisatin-loaded liposomes target the urokinase plasminogen activator system in breast cancer. Pharmaceutics, 12(7), 1-16. doi:10.3390/pharmaceutics12070641

Scopus Eid


  • 2-s2.0-85090731832

Start Page


  • 1

End Page


  • 16

Volume


  • 12

Issue


  • 7