Smart nanoparticle delivery systems for resveratrol: A targeted strategy to enhance anticancer efficacy and bioavailability

Abstract

Cancer remains a primary contributor to global mortality, driven by uncontrolled cell proliferation, metastasis, and resistance to standard chemotherapeutics. Resveratrol (RSV), a naturally occurring polyphenolic compound, exhibits strong anticancer potential through modulation of multiple signaling pathways including apoptosis, angiogenesis, and oxidative stress. However, its clinical translation is hampered by poor aqueous solubility, rapid metabolism, and limited systemic bioavailability. Smart nanoparticle-based delivery systems have emerged as a transformative strategy to overcome these limitations, enabling enhanced tumor accumulation, controlled release, and selective targeting via passive Enhanced Permeability and Retention effect (EPR effect) and active ligand-mediated mechanisms. This review critically summarizes recent advancements in RSV-loaded nanocarriers such as polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, and stimuli-responsive platforms used across diverse cancer models including colorectal, pulmonary, glioblastoma, and melanoma. Special focus is given to their physicochemical optimization, role in reversing multidrug resistance, minimizing systemic toxicity, and enabling co-delivery with conventional anticancer drugs. The review also outlines translational challenges, clinical outlook, and the future direction of RSV-based smart nanomedicine for precision oncology applications.