Development of Chrysin-loaded Zn@Metal Organic Framework (MOF) based Targeted Drug Delivery

Abstract

Therapeutic applications of chrysin, a natural flavonoid with potent anticancer and anti-inflammatory properties, are limited by its poor aqueous solubility and low bioavailability. To overcome these challenges, we developed a novel targeted drug delivery system using a zirconium-based metal-organic framework (Zn-MOF). The highly porous and stable Zn-MOF (UiO-66) was synthesized and characterized for its structural integrity, surface area, and drug-loading capacity. Chrysin was successfully encapsulated within the Zn-MOF with high loading efficiency (∼85%), as confirmed by XRD, FTIR, and TEM analysis. The chrysin@Zn-MOF exhibited pH-responsive sustained drug release, with significantly enhanced dissolution in acidic conditions mimicking the tumor microenvironment (∼75% release at pH 5.0 vs. ∼35% at pH 7.4). In vitro cytotoxicity studies demonstrated superior anticancer activity against MCF-7 breast cancer cells compared to free chrysin (IC50 reduced by ∼3.5-fold), attributed to improved cellular uptake confirmed by fluorescence microscopy. Surface modification with folic acid further enhanced targeted delivery to folate receptor-overexpressing cancer cells, increasing cellular internalization by ∼2.1-fold. Biodistribution analysis showed preferential accumulation in tumor tissues (∼5.8-fold higher than free drug), with minimal off-target distribution. Histopathological and biochemical assessments confirmed the biocompatibility of the Zr-MOF carrier. This study demonstrates that chrysin-loaded Zn-MOF represents a promising targeted delivery platform that enhances the therapeutic potential of chrysin while minimizing systemic toxicity, with broad applicability for other hydrophobic drugs.