Nanotechnological approaches in resveratrol delivery as a chemotherapeutic agent in cancer: advanced delivery strategies

Abstract

Resveratrol (RSV), a natural polyphenol found in grapes, berries, and peanuts, exerts anticancer effects through its antioxidant, anti-inflammatory, anti-proliferative, and pro-apoptotic actions, influencing major signaling pathways including p53, NF-κB, PI3K/Akt, and MAPK. Although these mechanisms position RSV as a promising chemotherapeutic adjunct, its clinical impact remains limited by low bioavailability, rapid metabolism, and poor systemic distribution. Advanced delivery approaches respond to these limitations by applying nanotechnology-based systems including nanoparticles, liposomes, and RSV-drug conjugates to improve its stability, strengthen pharmacokinetic performance, and enable targeted tumor delivery. Designing structural analogs through hydroxylation, methylation, and fluorination further refines pharmacodynamic properties. Preclinical studies show that RSV nanoformulations enhance tumor uptake, support controlled release, and increase therapeutic synergy, including reversing multidrug resistance when co-administered with agents such as docetaxel. However, clinical evaluation is still scarce and variable, underscoring the need for rigorous studies on dosing, safety, long-term performance, and translational feasibility. This review synthesizes current knowledge on RSV mechanisms, therapeutic potential, and nanotechnological delivery approaches, emphasizing the role of advanced delivery systems in maximizing its value in cancer therapy.