Berberine in Cancer Therapy: Emerging Role of Nanoparticle-Based Drug Delivery Systems

Cancer remains one of the leading causes of morbidity and mortality worldwide, prompting the continuous search for more effective and safer therapeutic options. Berberine, a natural isoquinoline alkaloid extracted from various medicinal plants such as Berberis species, has garnered significant attention for its multifaceted anticancer properties. It exerts potent cytotoxic effects against a wide range of cancer types by inducing apoptosis, inhibiting cell proliferation, modulating key signaling pathways, and suppressing angiogenesis and metastasis. However, the clinical application of berberine is considerably limited due to its poor aqueous solubility, low oral bioavailability, and rapid systemic elimination. To overcome these challenges, nanotechnology-based drug delivery systems have emerged as a promising strategy to enhance the therapeutic potential of berberine. Various nanoparticle formulations—such as polymeric nanoparticles, liposomes, solid lipid nanoparticles, nanoemulsions, and metallic nanoparticles—have demonstrated improved solubility, enhanced cellular uptake, sustained release, and targeted delivery of berberine to tumor tissues. Preclinical studies have reported superior anticancer efficacy and reduced systemic toxicity of these nanoformulations compared to free berberine. This review comprehensively explores the anticancer potential of berberine, its underlying mechanisms of action, and the advances in nanoparticle-mediated delivery systems. Emphasis is placed on recent developments in berberine-loaded nanocarriers, their pharmacological performance, and translational prospects. While significant progress has been made, further research is warranted to address formulation challenges, scale-up processes, and clinical validation. The integration of nanotechnology with berberine-based therapy holds considerable promise for the future of targeted and effective cancer treatment.