Targeted Delivery of Letrozole Using a Modified Metal-Organic Framework as a Promising Candidate in Breast Cancer Therapy

Metal-organic framework (MOF) can play a carrier role for an anticancer drug like letrozole (LTZ). This study reports an innovative and pH-responsive drug delivery system based on chitosan (CS) and folic acid (FA)-coated MOF. Higher cellular penetration can occur through higher folate receptors on the surface of cancer cells compared to normal cells. Firstly, ZIF-8@LTZ nanoparticles were successfully synthesized with an excellent loading efficiency of about 92%. LTZ was loaded into ZIF-8 ports and then capped with the CS-FA conjugate. The synthesized nanoparticles were characterized by Fourier transform infrared spectroscopy (FTIR), UV-visible spectroscopy, zeta potential analysis, X-ray diffraction (XRD), circular dichroism, dynamic light scattering (DLS), and scanning electron microscopy (SEM). 5-Diphenyltetrazolium bromide (MTT) assay was used to investigate the toxicity of synthesized nanoparticles, and apoptosis assay was used to investigate the mechanism of cell death after treatment with nanoparticles. In vitro release study confirms the controlled release of LTZ at high-performance acidic pH in cancerous media. About 75% of LTZ was released during 120 h at pH 5, and 60% and 49% drug release was obtained for pH 6 and pH 7.4, respectively. The cell culture results confirmed that ZIF-8@LTZ@CS-FA was more toxic than ZIF-8@LTZ, and it is more effective for targeting of positive receptor cells in breast cancer. The results of apoptosis analysis confirmed that LTZ and its ZIF-8 derivatives significantly promote the activity of caspase 3/7 enzymes in MCF-7 cells. Moreover, the engineered nanocarrier can be a very promising candidate for targeted and controlled cancer treatment.