Hyaluronic acid coating on the surface of curcumin-loaded ZIF-8 nanoparticles for improved breast cancer therapy: An in vitro and in vivo study

Despite developments in surgery and chemotherapy, effective treatment of breast cancer is still an urgent problem owing to recurrence and metastasis. By combining the advantages of curcumin (Cur), zeolitic imidazolate framework-8 nanoparticles (ZIF-8), and hyaluronic acid (HA) in breast cancer therapy, Cur-loaded and HA-coated ZIF-8 ([email protected]@HA) were synthesized using a method based on the pH-dependent solubility of Cur and the electrostatic interactions between zinc ions and carboxyl groups of HA. [email protected] were also prepared as a control group. Comprehensive comparisons of the physicochemical properties and anticancer activities of [email protected]@HA and [email protected] were conducted. The results indicated that the degradation of Cur during the synthesis of [email protected] was negligible. The obtained [email protected] and [email protected]@HA were truncated cubes with hydrodynamic diameters of 174 and 217 nm, respectively. [email protected]@HA possessed better stability during storage in different media, a slower drug release rate under neutral and acidic conditions, and a greater inhibitory effect on breast cancer than [email protected] For 4T1 cells, treatment using [email protected]@HA induced more cellular uptake and higher cytotoxicity, accompanied by higher lactate dehydrogenase release, cell cycle arrest in G2/M and S phases, production of reactive oxygen species, and apoptosis. In 4T1 tumor-bearing mice models, [email protected]@HA showed a stronger inhibitory effect on tumor growth and pulmonary metastasis. Therefore, [email protected]@HA might hold great potential as an agent for the effective therapy of breast cancer.