Atp-Responsive Polyethylenimine-Based Zinc-Ligand Nanoparticles for Gene Delivery Publisher



Mj Sabet Makkieh JAHANPEIMAY ; S Saeedi SARA ; B Kamali BABAK ; L Asadi LEILI ; Zs Biabanaki Zahra SADAT ; L Dastanpour LIDA ; Vh Lakhani Vahid HEIDARIPOUR ; Smk Mousavi Seyede Mahtab KAMRANI ; M Kiani MAHSA ; Aha Kelkawi Ali Hamad ABD
Source: Advances in Natural Sciences: Nanoscience and Nanotechnology Published:2025

Abstract

A zinc-coordinated ATP stimulus-responsive nanostructure was developed for CRISPR gene delivery. The system was based on low-molecular-weight polyethylenimine (PEI1.8k) attached to phenylboronic acid (PBA) and a pyridine zinc chelate. The nanostructure could form a polyplex with p-CRISPR DNA. The aim was for the PBA would bind to the ribose moiety of ATP and become hydrophilic, thus releasing the plasmid cargo. The in vitro findings demonstrated that the combination of a Zn-coordinated pyridine ligand, an ATP-sensitive PBA moiety, and a cationic backbone could act synergistically to condense DNA, enhance cellular internalization, disrupt endosomes effectively, and resist serum protein binding. This delivery platform enabled efficient CRISPR plasmid transfection in HEK 293T cells, even at low plasmid concentrations and under serum conditions ranging from 5% to 30%, outperforming the commonly used PEI25k. We suggest that this novel method has the potential to be an appropriate non-viral vector for CRISPR/Cas9 gene editing in vivo and that it may potentially have therapeutic significance. © 2025 Elsevier B.V., All rights reserved.