Encapsulating 2-Aminopyridine With Zeolite Imidazole Framework Nanoparticles for Induction of Cell Death via pH-Responsive Delivery in Hepatocellular Carcinoma (HepG2) Cells

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.

Keywords:

• 2-aminopyridine
• ZIF-8
• molecular docking
• drug release
• hepatocellular carcinoma

Author contribution

Conceptualization: AZ, TK, and ABS; Methodology: AZ, KC, MP, CC, KP, SS, MA, and KA; Software: AZ and KC; Validation: AZ, TK, and ABS; Formal analysis: AZ, KC, MP, and KA; Investigation: AZ; KC, SS, and CC; Visualization: AZ, MP, and KA; Resources: MP, TK, and ABS; Data curation: AZ and KA; Writing-original draft: AZ, KC, KA, and MP; Writing—review and editing: AZ, KC, TK, and ABS; Supervision: TK; Project administration: TK and ABS; Funding acquisition: TK. All authors have read and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by a Grant-aid from the Department of Biotechnology (DBT), BT/PR44695/NER/95/1880/2021.