The central bottleneck in nano-bio interactions lies in the dynamic protein corona (PC) that spontaneously forms on the surface of nanomaterials upon exposure to biological systems. The formation of PC redefines the biological identity of nanoparticles, thereby dictating key biological behaviors. Although it is well-known that PC formation is strongly regulated by the physicochemical properties of nanomaterials, how physicochemical properties of nanomaterials are translated into the specificity of PC protein recruitment and subsequent mediation of distinct biological functions remain elusive. Our team aims to dissect the dynamic regulatory network of PC formation and clarify the mechanisms governing the recruitment, assembly, and functional specialization of specific proteins in the PC for rational design of next-generation nanomedicine.

The detection of low-abundance protein biomarkers in biological fluids, such as serum, is a critical technical bottleneck in early cancer screening and diagnosis. Conventional proteomic approaches face challenges in achieving efficient detection of low-abundance targets due to interference from high-abundance proteins. The formation of the nanoparticle-protein corona in serum can specifically enrich low-abundance proteins while depleting high-abundance proteins, thereby significantly enhancing proteomic depth and offering a novel technical avenue for the discovery and detection of low-abundance biomarkers. Our group has developed the ProteoFish and ProteoFish-SELEX platforms for multiplexed pan-cancer diagnosis. We aim to develop a facile, cost-effective, and high-throughput detection platform for intelligent, multiplexed cancer screening in large-scale populations.

Efficient and selective in vivo delivery remains a critical bottleneck for nucleic acid therapeutics. Lipid nanoparticles (LNPs) rapidly acquire a dynamic and heterogeneous protein corona upon exposure to biological fluids. This corona can reprogram LNP biological identity, thereby reshaping cellular recognition, and ultimately organ tropism. However, current LNP discovery pipelines largely optimize chemical structure in isolation and rely on empirical screening. We are mapping the proteome atlas of LNP by integrating large-scale corona proteomics with chemical descriptors to systematically decode the network linking of LNP chemistry, corona signatures, and biological outcomes. We aim to develop new ionizable lipids with programmable organ targeting for next-generation LNP therapeutics.