ZIF-8 Nanocarrier-Based Co-Delivery of Curcumin and 5-Fluorouracil for Synergistic Antitumor Activity in Hepatocellular Carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly prevalent malignancy worldwide, posing a severe threat to human health. Although conventional chemotherapy remains a primary treatment modality, its clinical efficacy is limited by poor targeting, drug resistance, and systemic toxicity. To address these challenges, this study developed a zeolitic imidazolate framework-8 (ZIF-8)-based nanoplatform with pH-responsive behavior for dual-loading of 5-fluorouracil (5-FU) and curcumin (CUR). Methods: In this study, a ZIF-8-based nanoplatform with pH-responsive behavior was developed for the co-delivery of 5-FU and CUR. The ZIF-8@5-FU/CUR nanocomposite was comprehensively characterized to evaluate its structural stability, drug-loading capacity, and drug-delivery efficiency. Its antitumor activity was subsequently evaluated using in vitro and in vivo experimental models. Results: The ZIF-8@5-FU/CUR nanocomposite exhibited stable drug-loading properties and efficient co-delivery of 5-FU and CUR. In vitro experiments demonstrated significant cytotoxicity of the co-delivery system against HepG2 cells, resulting in extensive tumor cell death and superior antitumor activity compared with single-drug formulations. In vivo studies further showed that ZIF-8@5-FU/CUR effectively inhibited tumor growth by suppressing tumor cell proliferation, promoting apoptosis, and alleviating inflammation and oxidative stress. Moreover, the nanocomposite exhibited favorable biocompatibility. Conclusion: The ZIF-8@5-FU/CUR nanocomposite demonstrates potential as a safe and effective co-delivery system for HCC therapy. Its pH-responsive drug delivery and combined antitumor effects suggest that ZIF-8-based nanocarriers may provide a promising strategy for precision cancer therapy.