2026-06-30 中国科学院（CAS）
＜関連情報＞
- https://english.cas.cn/newsroom/research-news/202606/t20260625_1174791.shtml
- https://www.pnas.org/doi/10.1073/pnas.2521555123
非遺伝子工学的手法によるナノザイム近接標識により、ナノ粒子の細胞内相互作用ネットワークと輸送経路が明らかになる Nongenetic engineering nanozyme proximity labeling reveals subcellular in situ interactomes and trafficking pathways of nanoparticles
Chao Jiang, Yiyang Fu, Baichuan Jin, +7 , and Yuan Liu
Proceedings of the National Academy of Sciences Published:June 22, 2026
DOI:https://doi.org/10.1073/pnas.2521555123
Significance
Highly efficient delivery of nanomedicine hinges on deciphering nanoparticle (NP) interactions with biological systems. However, conventional methods disrupt native protein coronas and fail to capture in situ dynamic intracellular trafficking. Here, we introduce nanozyme proximity labeling (NPL), leveraging the peroxidase-like activity of iron oxide NPs to covalently tag proximal interacting proteins in situ. This genetic engineering-free strategy maps native NP-associated interactomes and trafficking pathways of NPs in live cells, capturing subcellular snapshots of dynamic interactions. Our study establishes NPL as a powerful platform to dissect nanomedicine–bio interfaces and will provide insights for the optimization of precision-targeted therapeutics.
Abstract
Elucidating the dynamic interactions between nanocarriers and cellular machinery is critical for advancing targeted nanomedicine. However, the optical microscopy imaging techniques can only provide a generalized view of nanomedicine localization. Proteomics approaches require cell lysis which disrupt native protein coronas during isolation, obscuring real-time intracellular trafficking mechanisms. Although proximity labeling enables in situ investigation of intracellular protein–protein interactions, it relies on genetically engineered enzyme fusion, thus limiting applicability across diverse systems. In this study, we report nanozyme proximity labeling (NPL), a genetic engineering-free strategy that harnesses the intrinsic peroxidase activity of Fe3O4 nanoparticles (NPs) to biotinylate proximal proteins within live cells. NPL achieves rapid biotinylation of NP-interacting proteins during intracellular transit. Using streptavidin pulldown and LC–MS/MS, we mapped high-fidelity in situ interactomes and suggested distinct trafficking pathways for mitochondrial-targeted Fe3O4@TPP NPs and nontargeted Fe3O4 NPs. Our NPL interrogates the native NP–protein corona–organelle interfaces, offering a generalizable platform to decipher subcellular targeting mechanisms and accelerate nanomedicine optimization.
