A Nanodrug-Enabled chemosensitization of cancer stem cells against tumor progression and metastasis

Abstract

Chemotherapy remains the primary treatment for tumors due to its systemic tumor-suppressing ability. However, the efficacy of chemotherapy is limited by drug resistance in cancer stem cells (CSCs), which play a crucial role in tumor progression and metastasis. In this study, we present a novel nanodrug that enhances the effectiveness of chemotherapy by simultaneously targeting CSCs in the tumor tissue and preventing tumor cells from transforming into CSCs. The nanodrug is formed through the self-assembly of doxorubicin (DOX) and the focal adhesion kinase (FAK) inhibitor PF-573228 (PF). Upon accumulation at the tumor site, DOX induces tumor cell death, while PF overcomes CSCs resistance to DOX by suppressing the level of tyrosine 397 phosphorylated FAK (FAK pY397) in CSCs. Furthermore, PF inhibits the acquisition of CSC phenotype in tumor cells by suppressing the process known as epithelial-mesenchymal transition (EMT). Consequently, the designed nanodrug exhibits a robust ability to address tumor progression and metastasis. This study provides a unique strategy to tackle the challenges posed by CSCs in cancer chemotherapy.