Interface Energy Tuning in Lanthanide Upconversion Nanoparticles through a Multilayer Growth Strategy

Conspectus Lanthanide-doped upconversion nanoparticles (UCNPs) have emerged as a revolutionary class of optical probes, converting low-energy near-infrared (NIR) photons into higher-energy visible or NIR emissions. This unique anti-Stokes process offers substantial advantages for biomedical applications including minimal autofluorescence interference and deep tissue penetration. Despite these promising features, the bioapplication of UCNPs was restricted by a critical bottleneck: low luminescence efficiency driven by severe surface-related quenching effects, such as the vibration of hydrogen–oxygen bonds. The advent of core–shell architectures has largely addressed this efficiency issue by passivating surface defects and shielding the core from environmental quenching. Nevertheless, conventional shell-growth strategies often lack the requisite atomic-level precision to strictly confine the doped ions, limiting their ability to construct well-defined interfacial structures. To fully realize the potential of UCNPs in advanced scenarios, such as multiplexed imaging, neuromodulation, and deep tissue sensing, we must move beyond simple surface passivation to address a more profound challenge: the directional control of interface energy transfer in a single nanoparticle. This necessitates precise control over doping ion interactions to effectively modulate spectral crosstalk, cross-relaxation, and inner-filter effects. To meet these demands, our group developed a one pot successive layer-by-layer (SLBL) strategy that enables the fabrication of multilayer nanostructures with atomic-level precision. This method provides an unprecedented tool for spatially segregating different lanthanide dopants, thereby transforming each interface into a programmable energy landscape. In this Account, we summarize our contributions to the field of multilayer UCNPs, centered on the concept of “interface energy tuning”. First, we introduce the principles and practical implementation of our versatile SLBL, leveraging precise reaction kinetics to manipulate the epitaxial growth of the shell layer. Next, we demonstrate how this approach enables the creation of a single nanoparticle capable of orthogonal trichromatic upconversion luminescence, facilitating groundbreaking applications in multiplexed optogenetic neuromodulation and NIR light vision to humans. We then shift our focus to the NIR window, especially the second near-infrared imaging window (NIR-II, 1000–2000 nm), detailing the unique design of novel Er 3+ -, Tm 3+ -, and Ho 3+ -sensitized UCNP systems endowed with NIR-II excitation, which is intrinsically unlocked by precise multilayer engineering. Finally, we highlight the in vivo applications of these advanced NIR-II probes, including real-time ratiometric biosensing, high-throughput multiplexed imaging, and dynamic visualization in animals. We believe that this Account will not only showcase the power of interface energy tuning but also provide a rational design framework for the next generation of programmable photonic nanodevices for cutting-edge biomedical research.