Phytochemicals and Their Nanoformulations for Targeting Hepatocellular Carcinoma: Exploring Potential and Targeting Strategies.

Hepatocellular carcinoma (HCC) continues to pose a global health concern, necessitating the exploration of innovative therapeutic approaches. In the recent decade, targeting tumor stroma consisting of extracellular matrix (ECM), immune cells, vascular system, hypoxia, and also suppressive mechanisms in HCC has attracted interest in repressing tumor growth and metastasis. Phytochemicals have attained considerable attention because of their manifold biological effects and high capacity for anticancer activities. These chemical agents have shown the capability to modulate different cells and secretions within the stroma of malignancies. In recent years, the development of nanoformulations has further enhanced the therapeutic potential of phytochemicals by improving their solubility, bioavailability, and targeted delivery to tumor tissues. This review aims to provide an encyclopedic overview of the potential of phytochemicals and their nanoformulations as promising therapeutic strategies for targeting HCC. The review initially highlights the broad array of phytochemicals exhibiting potent anticancer properties, including flavonoids, alkaloids, terpenoids, and phenolic compounds, among others. Then, the nanoformulations and modification of these agents will be reviewed. Finally, we will review the latest experiments that have examined the modulation of HCC using adjuvant phytochemicals and their nanoformulations.