Encapsulating 2-Aminopyridine With Zeolite Imidazole Framework Nanoparticles for Induction of Cell Death via pH-Responsive Delivery in Hepatocellular Carcinoma (HepG2) Cells
Azar Zochedh, Kaliraj Chandran, Karthick Arumugam, Mohana Priya, Murugan Anbazhagan, S. Asath Bahadur, Sureba Sukumaran, Cibe Chakaravarthy, Karthikeyan Palaniyandi, Thandavarayan Kathiresan
Abstract
The key objective for establishing a new drug delivery system is to transport therapeutic medications in the body’s circulatory system and deliver them to selected therapeutic spots. In the current study, 2-aminopyridine (2AP), a bioactive molecule, was wrapped around a metal oxide framework known as the Zeolite imidazole framework (ZIF-8) for efficient drug delivery in HepG2 cells. To begin with, an in-silico technique molecular docking to access the binding capability of 2AP with EGFR target, and it exhibited a score of −7.4 kcal/mol. The morphology of the nanoparticles was examined through SEM and TEM analysis, DLS and Zeta potential exhibited the particle size, stability and further elements and functional groups present in ZIF-8 and 2AP@ZIF-8 was examined through EDX, TGA, XRD, and FTIR analysis. The drug loading capacity of ZIF-8 was examined and the drug release efficiency of ZIF-8 for the delivery of 2AP was evaluated in the phosphate-buffered saline under different pH conditions and witnessed the pH-responsive and sustained drug release. The dose-dependent and time-dependent anticancer efficacy of 2AP@ZIF-8 nanoparticles treated HepG2 cells has been investigated through the in-vitro MTT assay method. The IC50 values of 2AP@ZIF-8 nanoparticles for 24, 48, and 72 h were observed to be 54.8, 48.5, and 45.3 μg/mL, respectively. The ZIF-8 and 2AP@ZIF-8 showed nontoxic to HEK293 cells. Overall, our findings showed that ZIF-8 offers a pH-responsive release of 2AP loaded and 2AP@ZIF-8 caused cell death in HepG2 cells, suggesting novel therapeutic approaches against hepatocellular carcinoma.