Sub-10 nm upconversion nanocrystals for long-term single-particle tracking

Xiaochen Qiu, Daoming Guan, Xiaojing Xia, Huan Ling, Jialing Hu, Yunxiang Zhang (), Emory Chan (), Fuyou Li () and Qian Liu ()
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Xiaochen Qiu: Fudan University
Daoming Guan: Fudan University
Xiaojing Xia: The Molecular Foundry, Lawrence Berkeley National Laboratory
Huan Ling: Fudan University
Jialing Hu: Fudan University
Yunxiang Zhang: Fudan University
Emory Chan: The Molecular Foundry, Lawrence Berkeley National Laboratory
Fuyou Li: Shanghai Jiao Tong University
Qian Liu: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: Abstract Lanthanide-doped upconversion nanoparticles are attractive single-molecule imaging probes due to their high photostability and anti-Stokes luminescence. However, achieving both small particle size and strong brightness has remained a major challenge, as reducing size often leads to dimmer emission. Herein, we fabricate a sub-10 nm cascade actively protected upconversion nanoparticles, which shows a 33-fold enhanced upconversion efficiency at the single-particle level compared to larger ~19 nm conventional nanoparticles. Theoretical modeling and time-resolved measurements show that emission loss mainly comes from energy leakage of Er3+ ions to surface defects. By introducing a NaYbF4 layer as photon-harvesting and protective intermediate layer, we minimize this energy loss and significantly boost brightness. A monolayer of inert NaLuF4 can effectively suppress the surface quenching to Yb3+. Using these ultra-small bright probes, we successfully tracked single epidermal growth factor receptor molecules on live cells for up to one hour, revealing dynamic switching between different diffusion modes.

Date: 2025
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DOI: 10.1038/s41467-025-64180-w

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