Folic acid-decorated tamoxifen-loaded covalent organic framework induces apoptosis in MCF-7 breast cancer cells via BAX/Caspase-8 upregulation.

Abstract

The side effects and non-specific targeting of healthy organs associated with conventional cancer therapies necessitate the design and fabrication of novel nanomaterial-based drug delivery systems. In this study, we successfully fabricated a novel two-dimensional (2D) covalent organic framework (COF) nanomaterial. This COF was loaded with tamoxifen (TMX) and surface-modified with folic acid (FA) to achieve effective targeting for breast cancer therapy. The resulting construct, TMX@COF-FA, was characterized using PXRD, FTIR, ¹³C NMR, CHNS analysis, BET surface area analysis, TGA, UV-Vis spectroscopy, SEM, and EDX analysis. The COF carrier demonstrated a high drug encapsulation efficiency of approximately 82%. Furthermore, it exhibited a pH-responsive drug release profile, with a significantly higher release rate at pH 5.4 compared to pH 7.4, which is ideal for the acidic tumor microenvironment. Cell viability studies revealed that TMX@COF-FA induced about 90% cell death in MCF-7 breast cancer cells, while showing minimal cytotoxicity in L929 fibroblast cells. The mechanism of cell death was investigated using AO/EtBr dual staining, ROS detection assays, flow cytometry (FACS), and qRT-PCR. Collectively, our findings demonstrate that the FA-conjugated COF can efficiently deliver TMX to MCF-7 cells via folate receptor-mediated endocytosis, leading to potent cancer cell destruction. This study underscores the potential of functionalized COFs as promising targeted drug delivery platforms for breast cancer treatment.