Enhancing Cancer Immunotherapy with Berberine and Its Loaded Nanoparticles: A Systematic Review

Neoplasms are considered a health problem around the world. This study systematically examines the effects of Berberine (BBR) and BBR-loaded Nanoparticles (NPs), with an emphasis on elucidating the molecular and cellular mechanisms through which these formulations enhance cancer immunotherapy.

A systematic literature search (on December 17, 2025) was conducted in PubMed, Scopus, Web of Science, and the Cochrane Library electronic databases. Related articles aligned with our study aim were screened, and the required data were extracted and recorded in a table. Moreover, the risk of bias for both in vitro and in vivo publications was assessed.

Finally, 22 studies were included in the screening process. BBR and its NPs potentially improved immunotherapy outcomes by reducing Programmed Cell Death 1 Receptor (PD-L1) expression (relieving PD-1/PD-L1-mediated immunosuppression), cytokine modulation, immune cell activation and infiltration, repolarization of macrophages from M2 to M1 phenotype, increasing T-cell-mediated cytotoxicity, disrupting mitochondrial membrane potential, and promoting the accumulation of intracellular Reactive Oxygen Species (ROS), inducing pyroptosis and immunogenic cell apoptosis in various cancerous cell lines. BBR NPs reduced systemic toxicity, improved sustained drug release, solubility, and drug targeting in tumor cells.

BBR and nanoformulated BBR enhance immunotherapy and drug delivery. However, limitations of this review were a lack of standardized study design techniques and clinical trial studies. Future studies should focus on cell toxicity, dose-effectiveness, and clinical translation.

BBR and its NPs showed favorable immunomodulatory properties and enhanced cancer immunotherapy in experimental studies. However, more clinical studies are needed in this field.