Homing Peptide-Based Targeting of Tenascin-C and Fibronectin in Endometriosis

Autor: Lorena Simón-Gracia, Kristina Kiisholts, Vilma Petrikaitė, Allan Tobi, Merli Saare, Prakash Lingasamy, Maire Peters, Andres Salumets, Tambet Teesalu
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Nanomaterials, Vol 11, Iss 12, p 3257 (2021)
Druh dokumentu: article
ISSN: 11123257
2079-4991
DOI: 10.3390/nano11123257
Popis: The current diagnostic and therapeutic strategies for endometriosis are limited. Although endometriosis is a benign condition, some of its traits, such as increased cell invasion, migration, tissue inflammation, and angiogenesis are similar to cancer. Here we explored the application of homing peptides for precision delivery of diagnostic and therapeutic compounds to endometriotic lesions. First, we audited a panel of peptide phages for the binding to the cultured immortalized endometriotic epithelial 12Z and eutopic stromal HESC cell lines. The bacteriophages displaying PL1 peptide that engages with angiogenic extracellular matrix overexpressed in solid tumors showed the strongest binding to both cell lines. The receptors of PL1 peptide, tenascin C domain C (TNC-C) and fibronectin Extra Domain-B (Fn-EDB), were expressed in both cells. Silver nanoparticles functionalized with synthetic PL1 peptide showed specific internalization in 12Z and HESC cells. Treatment with PL1-nanoparticles loaded with the potent antimitotic drug monomethyl auristatin E decreased the viability of endometriotic cells in 2D and 3D cultures. Finally, PL1-nanoparticless bound to the cryosections of clinical peritoneal endometriotic lesions in the areas positive for TNC-C and Fn-EDB immunoreactivities and not to sections of normal endometrium. Our findings suggest potential applications for PL1-guided nanoparticles in precision diagnosis and therapy of endometriosis.
Databáze: Directory of Open Access Journals