Trophoblast Cell Surface Antigen Imprinted Polymer Nanoparticles for Breast Cancer Therapy

Most breast cancers can be curable at an early stage with locoregional treatments, and the main therapeutic weapons in recurrence or metastatic situations are targeted therapies. In this context, the recent emergence of the glycoprotein TROP2 (trophoblast cell surface antigen 2) as a promising therapeutic target has led to therapeutic paradigms for treating patients with advanced or metastatic breast cancer. Here, we propose to develop, using a solid phase imprinting approach, fluorescent molecularly imprinted polymer nanoparticles containing the imprint of TROP2 epitopes acting as a key-hole system. These nanoparticles are small, spherical, very stable, and possess strong fluorescence. <i>In vitro</i> analyses using flow cytometry and confocal microscopy show that these nanoparticles are specifically bound to TROP2-overexpressing breast cancer cells. Furthermore, cell viability was performed to validate their cellular nontoxicity and biocompatibility. In addition, these nanoparticles efficiently penetrated 2D cultures and 3D spheroid breast cancer cell cultures. Overall, we have generated nontoxic MIP that specifically targeted TROP-2 overexpressed human breast cancer.