Co-delivery of epirubicin and letrozole using a metal-organic framework nanoparticle in breast cancer therapy

Combination chemotherapy is a viable approach for cancer treatment in clinics when dealing with multidrugresistant cancer. The difficulty of concentrating medications in drug-resistant cancers remains a substantial issue, making it challenging to get sufficient multi-drug delivery into tumour cells to enhance the synergetic therapeutic effect. To enhance combination therapy, we fabricated metal-organic framework (MOF) nanoparticles (NPs) that co-deliver letrozole (Let) and epirubicin (Epi). We created UIO-66@NH2-based MOFs to achieve desired encapsulation efficiencies of 82.93 +/- 2.13 for Let and 66.84 +/- 1.25 for Epi. The drug release profile revealed that the release rate of Let and Epi from the nanoparticles was pH-dependent, with a significant increase in acidic environments. This indicated the adaptive release capability of UIO-66-Let/Epi@NH2 in the breast cancer milieu. The nanoparticle size and entrapment efficiency were more stable at 4 degrees C as compared to 25 degrees C. Additionally, cellular assays demonstrated that a MOF loaded with Let and Epi increased the rate of apoptosis in MCF-7 cells compared to Let, Epi, and their combination (Let + Epi). The UIO-66-Let/Epi@NH2 group showed increased expression levels of Caspase3, Caspase9, and Mfn1 genes while the expression levels of MMP-3 and MMP-9 genes decreased. The effectiveness of the formulation in inducing apoptosis was confirmed by the results of DAPI staining microscopy and flow cytometry analysis. The higher apoptotic rate and toxicity of the Let/Epi-loaded UIO-66@NH2 MOF may be due to its greater delivery effectiveness into cancer cells. This article describes a novel MOF nanocarrier for the co-delivery of Let and Epi to treat breast cancer. The results demonstrate the potential of MOF nanocarriers as stimuli-responsive co-delivery systems for various drugs.