Folic acid-decorated chitosan nanoparticles co-delivering silymarin and docetaxel induce CDK-mediated cell cycle arrest and apoptosis in cervical cancer cell.

Globally, cervical carcinoma continues to rank within the top contributors to cancer-related fatalities for women, especially in low- and middle-income nations. In this work, silymarin (SIL) and docetaxel (DOC)-loaded chitosan nanoparticles decorated with folic acid (FA-CS NPs) (SIL-DOC@FA-CSNCs) targeting cervical cancer cells (HeLa cells) were created, and their synthesis, physicochemical properties, and anticancer activity were systematically assessed. Different characterization studies were used to confirm that SIL and DOC were successfully incorporated into chitosan nanoparticles. The fabricated SIL-DOC@FA-CSNCs exhibited an average particle size of 124.3 nm, a polydispersity index of 0.272 ± 0.01, and a positive zeta potential of +15.32 mV, indicating good colloidal stability, along with a high encapsulation efficiency of 96.12 ± 0.14% and a drug loading capacity of approximately 77.9%. Following a 24-h exposure to HeLa cervical cancer cells, the synthesised SIL-DOC@FA-CSNCs were tested for cytotoxicity using the MTT assay, and flow cytometry was used to investigate cell cycle progression. Combination index analysis demonstrated a strong synergistic interaction between SIL and DOC, with a CI value of 0.285. Additionally, RT-PCR studies verified that while the CDK blocker p21 was raised, important cyclin-dependent kinases (Cyclin D1 and CDK4) were decreased, indicating G0/G1 phase cell cycle arrest. Flow cytometric apoptosis analysis revealed increased early (13.11%) and late apoptotic (45.37%) cell populations, accompanied by elevated intracellular ROS generation. SIL-DOC@FA-CSNCs demonstrated significant antibacterial capacity, antioxidant capability, and considerable binding affinity towards CDK targets in molecular docking experiments. These findings suggest that SIL-DOC@FA-CSNCs represent a promising multifunctional nano-based therapeutic strategy for cervical cancer.