Amino-Functionalized Zn(II)-Based Trilinker Metal-Organic Frameworks Conjugated with Folic Acid for Targeted Delivery...

The development of stable, safe, and efficient carriers for targeted delivery of active pharmaceutical ingredients is a key focus in contemporary inorganic, medicinal, and materials chemistry. In the present study, a pH-responsive carrier was rationally designed based on an amino-functionalized Zn(II) trilinker metal-organic framework (MOF), [Zn₃(DAP)(BTC)₆(BTA)₃]_n^•4.425nDMF, abbreviated as NH₂-Zn-MUM-11 {MUM = Material from the University of Maragheh, 3,5-diaminopyridine (DAP), 1,3,5-benzenetricarboxylic acid (BTC), benzotriazole (BTA)}, and conjugated with folic acid (FA), to enable selective delivery of doxorubicin (DOX) as a model anticancer drug. The FA@NH₂-Zn-MUM-11 carrier demonstrated high biocompatibility, with no cytotoxic effects observed in normal breast epithelial cells (MCF-10A), while inducing significant cytotoxicity in human breast cancer cells (MCF-7). Under acidic conditions (pH 5.2), the system achieved nearly a 4-fold increase in drug release relative to physiological pH (97% vs 24%, respectively). Flow cytometry, the wound healing assay, and confocal laser scanning microscopy (CLSM) collectively demonstrated the system's ability to recognize cancer cells via folate receptor-mediated uptake, facilitate intracellular DOX release, and promote efficient cancer cell elimination. Hence, the obtained material might be further explored as a promising alternative for drug delivery.