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