Nanocarrier-mediated Delivery of Naringenin for Cancer Treatment: A Comprehensive Review

Introduction: Flavonoids derived from citrus fruits, particularly naringenin, have demonstrated significant anticancer, anti-inflammatory, and antioxidant properties. These biological activities allow naringenin to modulate crucial cellular mechanisms, including oxidative stress, inflammation, and apoptosis pathways. Nanocarriers such as liposomes, polymeric nanoparticles, dendrimers, and lipid-based systems are developed to elevate the solubility and bioavailability of naringenin, enable the controlled and extended release, and facilitate the targeted delivery to cancer tissues, while avoiding systemic toxicity. This review provides an overview of nanocarrier systems for naringenin delivery based on design principles and biological efficiency observed on pre-clinical models. Methods: A comprehensive search of databases (PubMed, Google Scholar, Web of Science, Traditional integrated knowledge resources, local dissertations, and books) was conducted up until September 2025 using key terms such as phytomedicine, naringenin, nanocarrier, and anticancer. Results: Preclinical studies have demonstrated that naringenin-loaded nanocarriers effectively enhance the therapeutic efficacy of naringenin compared to its free form. Improvements were observed in cellular uptake, pharmacokinetic profile, and tumor-targeting ability, leading to more pronounced anticancer effects in various experimental models. Discussion: The integration of nanocarrier technology in naringenin delivery represents a promising approach to overcome pharmacokinetic and pharmacodynamic challenges. However, several hurdles remain, including optimization of formulation parameters, large-scale reproducibility, and assessment of long-term safety. Conclusion: Naringenin-loaded nanocarriers have significant potential for cancer therapy, offering improved delivery and therapeutic performance. However, further research is essential to refine these delivery platforms, enhance their clinical translation, and establish their long-term safety and efficacy in humans.