Surface engineering of cell membrane biomimetic nanocomposites for enhanced drug lead discovery and evaluation

Cell membrane-coated nanoparticles (CMNPs) have garnered significant attention in drug lead discovery due to their superior biochemical properties and distinctive ability to target biological interfaces. However, designing nanocarriers that can expand the applicability of these emerging nanomaterials while preserving the biological functionality of the cell membrane remains a significant challenge. Herein, nucleus pulposus (NP) cell membrane biomimetic FITC-loaded poly-amidoamine (PAMAM) modified NiFe₂O₄-GO (NFGPFPs-NP) nanocomposites were prepared by purposeful surface engineering to facilitate the efficient screening of drug leads from Yaobitong capsule (YBTC) that target membrane receptors. By employing NFGPFPs magnetic fluorescent nanoparticles as cell membrane carrier materials, the synthesized NFGPFPs-NP were endowed with capabilities for magnetic separation and fluorescence in-situ imaging, thereby realizing the rapid screening of active compounds and the visual evaluation of their pharmacological activities. Meanwhile, the validation including adsorption capacity, selectivity and stability of this biomimetic screening platform had been evaluated, and demonstrated satisfactory results. Notably, the platform exhibited a high adsorption capacity, reaching up to 12.88 mg·g^-1 for the target bioactive compounds. Eventually, eight potentially bioactive compounds were screened out from YBTC, and their proliferative activity on NP cells were subsequently validated by pharmacological experiments and cell morphology fluorescence imaging assays. In conclusion, this purposeful surface engineering endowed CMNPs with significantly enhanced versatility, thereby expanding the application scope of cell membrane biomimetic platform.