Anticancer activity of curcumin-loaded nanocarriers: A focus on combined therapeutic modalities

Curcumin (CUR) is a polyphenolic compound known for its various therapeutic effects, including antioxidant, antiinflammatory, and anticancer activities. Researchers have elucidated several molecular and cellular pathways through which CUR exhibits potent anticancer activity, rendering it a promising candidate for cancer therapy. The activity of CUR is attributed to three reactive functional groups: the diketone moiety and two phenolic groups. Particularly, the presence of hydroxyl (OH) groups in the phenolic ring is responsible for CUR's anticancer effects. However, the therapeutic efficacy of CUR is restricted by its hydrophobic nature, rapid degradation with a short half-life, and low bioavailability. To address these challenges, researchers have developed nano-based drug carrier systems, such as nanoparticles, liposomes, and micelles, to encapsulate and deliver CUR effectively. These nanocarriers can be customized in size, chemical composition, surface charge, and functionalization to enable targeted delivery to specific sites. Also, the surface functionalities of nanocarriers can be tailored to specific targets, such as overexpressed receptors on cancer cells, leading to improved cellular uptake and therapeutic outcomes of CUR. Furthermore, integrating CUR-loaded nanocarriers with other therapeutic modalities, such as chemotherapy (CUR and chemotherapeutic agents coloaded), magnetic nanohyperthermia, photodynamic therapy, and nanocarrier-based ultrasound therapy, holds promise for enhancing treatment efficacy. This chapter provides an extensive overview of the molecular pathways and underlying mechanisms responsible for the substantial anticancer activity of CUR. In addition, it highlights the utilization of CUR-loaded nanocarriers in combination with other therapeutic modalities to achieve enhanced efficacy in cancer therapy. The combination of CUR with other modalities has demonstrated promising results in preclinical studies, indicating the potential for a synergistic effect.