None-Loss Target Release of Biomimetic CaCO3 Nanocomposites for Screening Bioactive Components and Target Proteins

Many traditional Chinese medicines have been clinically proven to have good anticancer effects in recent years. Tripterygium wilfordii, as a classic anticancer herbal medicine, has good effects, but its components are complex and its mechanism of action is unknown, which greatly limits its identification and wide application. In this study, we encapsulated nano-CaCO3 with a cell membrane to prepare biomimetic nanoparticles for screening bioactive molecules in T. wilfordii. These molecules can specifically bind to receptors on the cell membrane. Then bioactive molecules on this biomimetic CaCO3 nanosphere were immobilized to capture their target proteins and further study their potential signaling pathway. None-loss target release is primarily driven by CaCO3 nanosphere decomposition. As a result, we identified seven potential bioactive molecules from T. wilfordii. Among those, celastrol possesses the strongest anticancer activity. Meanwhile, with the help of the none-loss target release of the biomimetic CaCO3 nanocomposite, we further identified 39 potential target proteins. Further functional annotations and interaction network analysis of these captured proteins were carried out through protein databases; the P53 and G protein-coupled receptor signaling pathways were identified as potential signaling pathways for celastrol. Western blotting was then used to further confirm the effect of celastrol on the key proteins—P53 and MDM2—in the above signal pathways so as to explore the antitumor mechanism of celastrol. Our research demonstrates that this biomimetic CaCO3 nanocomposite is an ideal affinity screening platform and it can screen the bioactive molecules and their target proteins through a way of none-loss target release.