Core-Shell Nanostructured Drug Delivery Platform Based on Biocompatible Metal-Organic Framework-Ligated Polyethyleneimine for Targeted Hepatocellular Carcinoma Therapy

Multifunctional nanosized metal-organic frameworks(NMOFs)have advanced rapidly over the past decade to develop drug deliverysystems (DDSs). These material systems still lack precise and selectivecellular targeting, as well as the fast release of the quantity ofdrugs that are simply adsorbed within and on the external surfaceof nanocarriers, which hinders their application in the drug delivery.Herein, we designed a biocompatible Zr-based NMOF with an engineeredcore and the hepatic tumor-targeting ligand, glycyrrhetinic acid graftedto polyethyleneimine (PEI) as the shell. The improved core-shellserves as a superior nanoplatform for efficient controlled and activedelivery of the anticancer drug doxorubicin (DOX) against hepaticcancer cells (HepG2 cells). In addition to their high loading capacityof 23%, the developed nanostructure DOX@NMOF-PEI-GA showed an acidicpH-stimulated response and extended the drug release time to 9 daysas well as enhanced the selectivity toward the tumor cells. Interestingly,the DOX-free nanostructures showed a minimal toxic effect on bothnormal human skin fibroblast (HSF) and hepatic cancer cell line (HepG2),but the DOX-loaded nanostructures exhibited a superior killing effecttoward the hepatic tumor, thus opening the way for the active drugdelivery and achieving efficient cancer therapy applications.

Automated summary

By grafting glycyrrhetinic acid to polyethyleneimine, a biocompatible Zr-based metal-organic framework was designed for efficient controlled drug release and selective targeting against hepatic cancer cells. The improved core-shell structure enhanced the drug loading capacity and selectivity towards tumor cells, while exhibiting minimal toxicity to normal cells. This study provides a new approach for active drug delivery and efficient cancer therapy applications.