Nickel-Induced Cardiotoxicity: Immunopathogenesis, Thromboinflammation, and a Targeted Nanotherapeutic Strategy Publisher Pubmed



Joghataie P ; Habibi Z ; Bahrampour A ; Danjeh M ; Molaee P ; Yousefi Chermehini N ; Forouzin S ; Zamanifard S ; Nikdoust F
Source: International Immunopharmacology Published:2026

Abstract

Nickel (Ni) is a pervasive environmental toxicant found in contaminated water, soil, and airborne particulates. Even at low doses, Ni accumulates in the body through inhalation, ingestion, or dermal contact, causing progressive systemic injury. The cardiovascular system is particularly vulnerable, where Ni induces sustained oxidative stress, endothelial dysfunction, platelet hyperactivation, platelet–leukocyte aggregation, and NETosis, collectively creating a pro-thromboinflammatory state that heightens thromboembolic risk. At the molecular level, Ni perturbs calcium signaling, elevates intracellular ROS, and disrupts ion channel homeostasis, impairing cardiomyocyte viability and regenerative capacity. Current strategies, including conventional chelation, gene therapy, and nanoparticle interventions, partially reduce systemic Ni burden but fail to fully neutralize intracellular Ni or halt chronic vascular inflammation. To overcome these limitations, we developed a P-selectin–targeted nanoparticle (NP) platform that homes to activated endothelium and platelets at sites of vascular injury. These multifunctional NPs deliver a synergistic payload of antioxidants (to neutralize ROS), anti-inflammatory agents (to suppress vascular inflammation), and SHP-1 (to promote efferocytosis and plaque stabilization). This multi-pronged approach simultaneously mitigates acute Ni-induced injury, suppresses chronic thromboinflammation, and promotes cardiovascular repair. Our findings establish a comprehensive therapeutic framework for Ni-induced cardiotoxicity, offering a precision strategy with potential applicability across diverse vascular inflammatory disorders. © 2025 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.