Curcumin and doxorubicin encapsulated in biocompatible clay‐based nanomaterial: A strategy to overcome multidrug resistance

Multidrug resistance (MDR) due to the overexpression of the P‐glycoprotein (P‐gp) efflux pump remains a significant challenge in cancer therapy, also in breast cancer. Traditional pharmacological approaches have focused on using inhibitors to modulate P‐gp expression and function. Curcumin, a polyphenol derived from Curcuma longa L., is one of the most extensively studied natural compounds with the potential as an effective P‐gp inhibitor. Despite its promising attributes, the clinical application of P‐gp inhibitors is complicated by P‐gp's presence in healthy cells, such as those in the intestinal barrier and blood–brain barrier, which can lead to increased toxicity. To address these challenges, we developed a novel multifunctional nanomaterial by covalently bonding halloysite nanotubes (HNTs) with hectorite (Ht) and loading it with curcumin and doxorubicin. The efficacy of the co‐delivery of curcumin and doxorubicin by HNTs‐Ht nanomaterial was evaluated by cytotoxicity assays on MCF‐7R cells, both in two‐dimensional (2D) and in three‐dimensional (3D) models. The obtained data show that curcumin causes increased doxorubicin accumulation by acting as a substrate for P‐gp transport and as a stimulator of the adenosine triphosphate (ATP)‐dependent drug efflux transporter on a doxorubicin‐resistant breast cancer cell line. The results suggest that the HNTs‐Ht nanomaterial could provide a promising approach to improve chemotherapy effectiveness by overcoming MDR and enhancing treatment outcomes.