Cell Membrane-Camouflaged Biomimetic Magnetic Fluorescent\nNanoparticles with Enhanced Stability for High-Performance Lead Drug\nDiscovery

Biomimetic\nnanoengineering empowers nanoparticles with enhanced\nbiointerfacial capabilities by directly utilizing cell membranes (CMs)\nof natural origin. This top-down technique provides a powerful tool\nfor the screening of potentially active compounds in complex matrices.\nHerein, cartilaginous end plate (CEP) cell membrane biomimetic Nile\nred (NR)-loaded zeolitic imidazolate frameworks-8 (ZIF-8) modified\nmagnetic graphene oxide (CEP/MGO-ZIF-8-NR) nanocomposites with enhanced\nstability were accurately prepared by chemical bonding and used as\na drug discovery platform for the specific identification and effective\nextraction of drug leads with anti-intervertebral disc degeneration\n(IDD) in Yaobitong capsules (YBTCs). The constructed CEP/MGO-ZIF-8-NR\nexhibited excellent magnetic properties, fluorescence properties,\nand stability. In addition, drug binding experiments showed that the\nCEP/MGO-ZIF-8-NR nanocomposites possessed higher adsorption capacity,\nfaster adsorption rate, and superior selectivity compared with uncoated\nMGO-ZIF-8-NR. Ultimately, four potential bioactive molecules, including\nginsenoside Ro, ginsenoside Rg1, astringin, and chikusetsusaponin\nV methyl ester, were successfully screened and identified in vitro\nfrom YBTC. The results of the CCK-8 assay and BrdU ELISA kit showed\nthat the screened compounds promoted CEP cell proliferation in a concentration-dependent\nmanner. Cellular distribution experiments revealed that CEP/MGO-ZIF-8-NR\ncould rapidly escape from lysosomes and into the cytoplasm. And the\npharmacological activity of these compounds was further confirmed\nby real-time cytomorphological imaging of CEP cells by confocal laser\nscanning microscopy (CLSM). Overall, this surface engineering strategy\nendows bioaffinity sample pretreatment materials with tremendous versatility,\nimproves drug screening efficiency, and broadens the horizons and\nmethodologies for drug lead discovery.