Biomimetic phycocyanin lipid-based nanoparticles ameliorate placental dysfunction and restore angiogenic balance in a pre-eclampsia model.

Pre-eclampsia (PE) is a life-threatening pregnancy disorder associated with substantial maternal and fetal morbidity and mortality worldwide. Despite its clinical significance, current treatment strategies remain largely limited to symptomatic management, underscoring the urgent need for targeted interventions that address underlying pathophysiology. Lipid-based nanoparticles (LBNPs) have emerged as promising platforms for placental drug delivery. However, achieving precise and efficient site-specific accumulation remains a major challenge. Herein, we developed trophoblast cell membrane-hybridized, phycocyanin (PC)-loaded lipid-based nanoparticles (LBNP-PC@M) to enhance placental targeting. By integrating the intrinsic bioactivity of phycocyanin with the biomimetic targeting capability of trophoblast membranes, LBNP-PC@M facilitates preferential accumulation in the placenta and subsequent localized release of the therapeutic cargo, thereby improving angiogenic balance and metabolic homeostasis. In an inflammation-induced PE model, LBNP-PC@M treatment enhances placental vascularization, mitigates fetal growth restriction, and alleviates key pathological features associated with PE. Multi-omics analyses, including transcriptomics and metabolomics, indicate that LBNP-PC@M modulates pathways related to angiogenesis, oxidative stress responses, and amino acid metabolism, while partially restoring dysregulated histamine metabolism in PE placentas. Collectively, this study presents a biomimetic nanoplatform for placenta-targeted delivery of bioactive compounds, offering a promising strategy for modulating placental dysfunction and advancing therapeutic approaches for PE and related placental disorders.