Hybrid nanoparticles coated with hyaluronic acid lipoid for targeted co-delivery of paclitaxel and curcumin to synergistically eliminate breast cancer stem cells.

Conventional chemotherapy drugs such as paclitaxel (PTX) can effectively inhibit tumor growth by killing the majority of the proliferating cancer cells; however, it also results in multi-drug resistance (MDR) and facilitates the conversion of non-cancer stem cells (non-CSCs) to cancer stem cells (CSCs), which are considered the reason for chemotherapy resistance, relapse, and metastasis. Thus, exploring combination therapy with multiple chemotherapeutics is considered as a promising approach for simultaneously eliminating CSCs and non-CSCs. Here, we fabricated a bCSC (breast cancer stem cell)-targeting co-delivery system (HA-hybrid NPs) by attaching a lipoid (HA-HDA) to the surface of hydrophobic PLGA nanoparticles to co-deliver the widely used chemotherapy agent, PTX, and the selective inhibitor of CSCs, curcumin (CUR). This co-delivery system was capable of targeting bCSCs via an interaction between HA and the CD44 receptor on the membrane of bCSCs, and it could efficiently eliminate the bCSC population, decrease the mammosphere formation of bCSCs, and inhibit the migration of bCSCs. Most importantly, HA-hybrid co-delivered NPs exhibited enhanced anti-tumor efficacy by synergistically inhibiting the growth of both non-bCSCs and bCSCs on MCF7 xenografted tumor models. Taken together, the results of this study demonstrate that this bCSC-targeted HA-hybrid NP provides a potential strategy for enhancing breast cancer therapeutic efficiency.