ナノ粒子の細胞内輸送経路を可視化する新手法を開発（Scientists Develop Novel Method for Mapping Intracellular Pathways of Nanoparticles）

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

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.