Programmed Co-delivery of tamoxifen and docetaxel using lipid-coated mesoporous silica nanoparticles for overcoming CYP3A4-mediated resistance in triple-negative breast cancer treatment
Yinan Wang, WeiYi Cheng, Jingjing Zhu, He Li, WeiYe Ren, Dandan Bao, Ji‐Gang Piao
Abstract
PURPOSE: This study aims to revolutionize the treatment of aggressive triple-negative breast cancer (TNBC), notorious for its resistance to standard therapies. By ingeniously combining Tamoxifen (TMX) and Docetaxel (DTX) within a lipid-coated mesoporous silica nanoparticle (LP-MSN) delivery system, we intend to enhance therapeutic efficacy while circumventing DTX resistance mediated by CYP3A4 expression. METHODS: We rigorously tested TNBC cell lines to confirm the responsiveness to Docetaxel (DTX) and Tamoxifen (TMX). We adeptly engineered LP-MSN nanoparticles and conducted a thorough examination of the optimal drug release strategy, evaluating the LP-MSN system's ability to mitigate the impact of CYP3A4 on DTX. Additionally, we comprehensively analyzed its pharmacological performance. RESULTS: Our innovative approach utilizing TMX and DTX within LP-MSN showcased remarkable efficacy. Sequential drug release from the lipid layer and mesoporous core curbed CYP3A4-mediated metabolism, substantially enhancing cytotoxic effects on TNBC cells without harming normal cells. CONCLUSION: This pioneering research introduces a breakthrough strategy for tackling TNBC. By capitalizing on synergistic TMX and DTX effects via LP-MSN, we surmount drug resistance mediated by CYP3A4. This advancement holds immense potential for transforming TNBC treatment, warranting further clinical validation.