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Synthesis and characterization of a PDMS-PMOXA based polymersomes sensitive to MMP-9 for application in breast cancer

Porta, Fabiola and Ehrsam, Daniel and Lengerke, Claudia and Meyer Zu Schwabedissen, Henriette E.. (2018) Synthesis and characterization of a PDMS-PMOXA based polymersomes sensitive to MMP-9 for application in breast cancer. Molecular pharmaceutics, 15 ((11)). pp. 4884-4897.

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Official URL: https://edoc.unibas.ch/67827/

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Abstract

Cytotoxic compounds used to treat cancer are often associated with adverse events. The development of formulations activated by tumor-specific triggers would allow a reduction of systemic exposure while maintaining therapeutic concentrations in the tumor. One enzyme with proteolytic activity reported to be involved in tumor progression and assumed to be enhanced in the tumor environment is the matrixmetalloproteinase 9 (MMP-9). In our study, we aimed to develop surface modified PDMS-PMOXA polymersomes able to release their cytotoxic payload upon digestion by MMP-9. To test the applicability of such a system in breast cancer, this tumor entity was assessed for MMP-9 expression, supporting breast cancer as a potential target. The surface-modified polymersomes were synthesized and formulated resulting in paclitaxel loaded particles of about 320 ± 153.15 nm in size with a surface potential of 0.04 ± 0.007 mV. After verifying expression and activity of MMP-9 in MCF7 cells, this cell line was used for further analysis. Treatment of MCF7 cells with the polymersomes significantly reduced cell viability, this effect was abolished after addition of MMP-inhibitors, suggesting proteolytic activation. In zebrafish embryos, the polymersomes were observed in the circulation with some enrichment in liver and agglomerates in the caudal veins. Importantly, in zebrafish embryos xenografted with mKate2-expressing MCF7 cells the amount of tumor cells, quantified by detecting the copies of the heterologously expressed fluorescent protein, significantly decreased after treatment with PDMS-PMOXA-SRL paclitaxel polymersomes. Taken together our data suggest that polymersomes modified with an MMP-9 labile peptide and loaded with paclitaxel can be formulated, and that these particles exert pharmacological activity upon enzymatic digestion.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Biopharmazie (Meyer zu Schwabedissen)
UniBasel Contributors:Meyer zu Schwabedissen, Henriette and Porta, Fabiola and Ehrsam, Daniel
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1543-8392
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:23 Apr 2020 15:43
Deposited On:23 Apr 2020 15:43

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