Cell membrane-coated functionalized mesoporous silica nanoparticles for screening potential anti-cancer natural products.

A novel cell membrane-based biomimetic screening platform was developed for in vitro discovery of potential anti-cancer compounds. HepG2 cell membranes with biological recognition functions were stably immobilized onto aldehyde-functionalized mesoporous silica nanoparticles (HepG2-CM@AFMSNs) to enable affinity capture of potential anti-hepatocellular carcinoma (anti-HCC) compounds from herbal extracts. Specifically, the aldehyde-functionalized mesoporous silica was conjugated with HepG2 cell membranes via glutaraldehyde crosslinking, which could effectively prevent membrane shedding and preserve the inherent bioactivity. Natural products captured by HepG2-CM@AFMSNs were dissociated from the cell membranes, and structural identification was performed on eluents using matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). The reproducibility and stability of HepG2-CM@AFMSNs were significantly improved by optimizing the conditions for cetyltrimethylammonium bromide (CTAB) removal, ultrasonic cell disruption, and membrane immobilization. As a result, four potential anti-HCC compounds, i.e., tenacissoside H, scutellarin, emodin, and baicalin, were screened from three herbal extracts, and their anti-proliferative effects on HepG2 cells were verified by MTT assay. Overall, the developed HepG2-CM@AFMSNs combined with MALDI MS analysis demonstrated significant advantages in screening natural products with anti-cancer potential from herbal extracts.