Drug-target recognition has great impacts on revealing
mechanisms
of pharmacological activities, especially drug resistance and off-target
effects. In recent years, chemoproteomics has been widely used for
drug target screening and discovery due to its high-throughput, high
accuracy, and sensitivity. However, there still remain challenges
on how to efficiently and unambiguously track target proteins from
complex biological matrices. Herein, we report a drug target screening
method based on virus-like iron-gold heterogeneous nanoparticles (Au@Fe3O4 NPs). The unique structure of Au@Fe3O4 NPs not only maintains the magnetism of Fe3O4 NPs to facilitate protein enrichment and purification,
but also increases drug modification by introducing more active sites
on the surface of Au NPs. After coincubating the drug modified NPs
with the cell lysate, the high loading of drug on the surface of Au@Fe3O4 NPs was beneficial for capturing target proteins
with low abundance. This well-designed heterogeneous nanomaterial
provides a novel strategy for improving the efficiency and accuracy
of affinity-based proteomics.