In Silico Design of Zinc-Aptamer Network Nanoparticles for Breast Cancer treatment

Metal-biomolecule network nanoparticles (MBN NPs) are hybrid nanostructures that exploit metal-biomolecule coordination to achieve tunable stability, biocompatibility, and biofunctionality. In this study, a computational strategy was developed to design zinc-based MBN NPs incorporating the anti-EGFR RNA aptamer CL۴ for potential use in breast cancer therapy. The three-dimensional structure of CL۴ was predicted using AlphaFold and extended to nanoparticle-level assemblies consisting of ۳۰-aptamer constructs. Six structural models were generated, including single and ۳۰-aptamer assemblies in zinc-free and zinc-incorporated states. Zinc atoms were introduced either by a custom Python script or directly through AlphaFold prediction, and all structures were energy-minimized using YASARA. Docking simulations were then performed against the extracellular domain of wild-type EGFR (PDB ID: ۳NJP) using HDOCK. The analysis revealed that the ۳۰-aptamer assemblies bound more strongly to EGFR than the single CL۴ aptamers, and zinc incorporation further enhanced structural stability and receptor recognition. The AlphaFold-predicted zinc-incorporated ۳۰-aptamer construct demonstrated the best performance with a docking score of -۳۸۳.۵ and confidence of ۰.۹۹. These findings suggest that zinc-mediated network formation can stabilize aptamer assemblies and improve their binding affinity, providing a rational in silico foundation for the development of zinc-based CL۴ nanotherapeutics for breast cancer.

کلیدواژه ها:

metal-biomolecule network nanoparticles ، CL۴ aptamer ، EGFR ، breast cancer ، Molecular docking ، Nanobiotechnology