Dual-Action Cellular Nanoparticles for Effective Lead (Pb²⁺) Detoxification.

Abstract

Lead (Pb²⁺) exposure remains a persistent and serious public health concern due to its widespread presence and profound toxicity. Building on recent advances in toxin-neutralizing cell membrane-coated nanoparticles (CNPs) and the discovery of Pb²⁺-binding DNA aptamers, we develop dual-action neuron-mimetic CNPs for effective Pb²⁺ detoxification. In the formulation, the CNPs encapsulate aptamers within metal-organic framework (MOF) cores and coated with membranes derived from SH-SY5Y neuroblastoma cells, two functional components working together to neutralize Pb²⁺. The resulting constructs, termed Neuron-MOF/aptamer-NPs, exhibit strong Pb²⁺ binding capacity, excellent colloidal stability in physiological media, and resistance to DNA leakage. <i>In vitro</i> assays identify Neuron-MOF/aptamer-NPs as the most potent formulation, demonstrating dual-action neutralization against Pb²⁺-induced toxicity, oxidative stress, and lipid peroxidation in SH-SY5Y cells. <i>In vivo</i>, Neuron-MOF/aptamer-NP treatment significantly improves survival in a mouse model of lead poisoning and reduces hematologic, hepatic, and renal damage. Behavioral assessments further confirm the restoration of spatial memory and locomotor function. Neuron-MOF/aptamer-NPs exhibit no signs of acute toxicity in healthy mice. These findings establish Neuron-MOF/aptamer-NPs as a potent and biocompatible therapeutic platform for targeted lead detoxification with systemic and neuroprotective benefits.