Self-assembly of phosphorylated capsaicin and curcumin for treatment of triple-negative breast cancer via combination of chemotherapy and photodynamic therapy

Natural products showed many benefits for human health and are important resources in drug discovery and herbal medication development. However, their pharmacological activities are often constrained by their poor water solubility. To address these challenges, various drug delivery systems (DDS) have been developed to enhance the physicochemical properties of drugs, thereby improving their pharmacological effects or reducing adverse effects. In this study, we reported the construction of a novel natural products-based DDS through a self-assembly engineering approach, in which curcumin (Cur) was encapsulated by phosphorylated capsaicin (Cap-p). The physicochemical properties, drug loading and release behavior as well as therapeutic effects of Cap-p and Cap-p@Cur were investigated in detail. Results demonstrate that both Cap-p and Cap-p@Cur can self-assemble into nanovesicles and exhibit high water dispersibility. Results from biological assays suggested Cap-p exerts favorable biocompatibility toward MDA-MB-231 cells at concentration of 40   µg/mL. Compared to free Cur and Cap-p, Cap-p@Cur displays obviously enhanced cell killing capability against MDA-MB-231 cells and its cell killing ability was significantly amplified upon light irradiation. In addition, Cap-p displayed obvious bone-targeting capability, indicating its potential for eradicating bone-metastasis of triple-negative breast cancer (TNBC). The above results suggest that Cap-p@Cur holds considerable promise in treatment of TNBC via combining chemotherapy and photodynamic therapy. This work will provide some valuable insights into construction of natural product-based carrier-free DDS.