Natural-product-modified smart nanocarrier enabling Fe ³ ⁺ fluorescence sensing and targeted delivery of ligustrazine for alzheimer’s disease intervention

Alzheimer’s disease (AD) is closely associated with dysregulated brain iron metabolism and oxidative neuronal damage. Herein, we report a multifunctional nanoplatform (
CS-1@CP1@LZ
) based on a natural-product-modified chitosan carrier integrated with a structurally stable luminescent Metal–organic framework (MOF) core (
CP1
) and the neuroprotective molecule ligustrazine (LZ). The resulting
CS-1@CP1@LZ
exhibits favorable physicochemical stability, suitable surface charge, and high drug-loading efficiency. Owing to the Fe
3
⁺-responsive coordination environment of CP1, the nanoplatform displays a ratiometric dual-emission fluorescence response with high sensitivity, selectivity, and recyclability for Fe
3
⁺ detection under physiological conditions, demonstrating its feasibility as an iron-responsive fluorescent system. In an Aβ-induced SH-SY5Y (human neuroblastoma SH-SY5Y cell line) cell injury model,
CS-1@CP1@LZ
significantly restored intracellular redox balance by elevating the activities of catalase (CAT) and total superoxide dismutase (T-SOD), and glutathione (GSH) levels, while enhancing neurotrophic support through the upregulation of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In addition, increased expression of the Aβ-degrading enzyme insulin-degrading enzyme (IDE) was observed, suggesting a potential contribution to Aβ clearance at the cellular level. Overall, these findings indicate that
CS-1@CP1@LZ
integrates iron-responsive fluorescence sensing and neuroprotective activity within a single nanoplatform, providing a proof-of-concept strategy for the development of ferroptosis-related AD-relevant nanomaterials.