Enhanced targeted drug delivery to hepatocellular carcinoma using Cucurbit[6]uril-modified ZIF-8 nanoparticle

J Biomater Appl. 2024 Dec 7:8853282241306836. doi: 10.1177/08853282241306836. Online ahead of print.

Abstract

Building on our innovative approach to combatting cancer, this study explores the development of a sophisticated hybrid nanocarrier system leveraging the unique properties of allyl oxide cucurbit[6]uril with galactose clusters (AOQ[6]@Gal) to modify ZIF-8 nanoparticles. These nanoparticles are designed to encapsulate and efficiently deliver the anticancer drugs doxorubicin (DOX) and curcumin (CUR), enhancing their water solubility and stability, while also providing active targeting towards hepatocellular carcinoma cells. The comprehensive characterization of AOQ[6]@Gal@ZIF-8@Drug nanoparticles revealed promising outcomes, including drug loading efficiencies of 9.7% for DOX and 8.3% for CUR, alongside a pH-responsive release profile that ensures effective drug delivery in the tumor microenvironment. Cytotoxicity studies underscored the hybrid system's superior safety profile, exhibiting minimal toxicity towards normal hepatocytes HL7702 and pronounced cytotoxic effects against hepatocellular carcinoma cells HepG2. These results highlight the hybrid nanocarrier's potential as a targeted, efficient, and safe platform for the delivery of chemotherapy agents in the treatment of liver cancer.

Keywords: Metal-organic frameworks (MOFs); chemotherapeutic drugs; multivalent effects; pH-responsive; targeted therapy.