Synthesis and Application of Zr MOF UiO-66 Decorated with Folic Acid-Conjugated Poly Ethylene Glycol as a Strong Nanocarrier for the Targeted Drug Delivery of Epirubicin

Abstract

The problems that drug delivery systems (DDSs) frequently have—such as restricted drug loading capacity and uncontrolled drug release—can be addressed by metal organic frameworks (MOFs). In the current study, we investigate the development of Zr metal-organic framework (MOF) UiO-66 nanoparticles coated with folic acid-conjugated polyethylene glycol (UIO-66-EPI@PEG-FA) as a targeted delivery of Epirubicin (EPI) to breast cancer cells. A significant encapsulation efficiency was seen in the UIO-66-EPI@PEG-FA nanoparticles (75.33 ± 1.34%). The patterns of drug release demonstrated the pH-dependent behavior of the nanoparticle, with a release of approximately 62.6% at acidic pH (5.4) over 24 h, compared to 47.2% at physiological pH (7.4). As evidenced by flow cytometry results, apoptosis rate induced in MCF-7 cells by UIO-66-EPI@PEG-FA (40.9%) was found to be higher than that induced by free EPI (23.03%). Furthermore, wound healing assay showed that UIO-66-EPI@PEG-FA successfully inhibited cell migration, consolidating its role in preventing cancer progression. As evidenced by polymerase chain reaction (PCR) assay, by decreasing the MMP-2 and MMP-9 genes’ expression levels as well as significant upregulation of pro-apoptotic markers (caspase-3, caspase-9, and mitofusin-1), the UIO-66-EPI@PEG-FA inhibited the growth of the malignancy by activating both intrinsic and extrinsic apoptotic pathways. DAPI-stained microscopy verified the flow cytometry study’s results, showing that the produced nanoparticle successfully induced death in cancer cells. The prepared MOF showed a notable selectivity for MCF-7 cancer cells and showed no discernible adverse effects on the MCF-10 A normal breast cell line. These findings provide important insights into the development of UIO-66-Epi@PEG-FA for targeted cancer treatment. However, developing a unique medicinal strategy requires extensive research, clinical trials, and regulatory procedures.

Graphical Abstract