NIR Luminescent Nd-Doped LuPO₄ Nanoparticles for In Vivo Imaging

Bioimaging using luminescent probes aids in diagnostics and monitoring disease progression across various conditions. Organic luminophores are commonly employed for sentinel lymph node mapping, tumor imaging, and for guiding tumor resection. However, their clinical application is limited by susceptibility to photobleaching and concentration-dependent quenching. In contrast, luminescent nanoparticles (NPs) offer brighter luminescence, minimal photobleaching, and can be functionalized to target specific tissues or pathogens. Additionally, they can serve as drug carriers, enabling multimodal use for both imaging and therapeutic purposes.

Recently, nanoparticles doped with lanthanide (La) ions have gained interest for luminescent applications due to their tunable spectral properties. In particular, neodymium (Nd) ions are attractive for in vivo imaging because of their strong emission in the near-infrared II (NIR-II) spectral region, where body tissues and fluids are largely transparent. Nd-doped BiVO₄ NPs have demonstrated strong emission with detection depths of up to 20 mm in vivo, while demonstrating significantly lower photobleaching than clinically used organic fluorophores.

Our work focuses on NIR-emitting Nd-doped LuPO₄ nanoparticles synthesized via flame spray pyrolysis, a highly scalable and reproducible nanomanufacture method capable of producing a variety of high-quality nanoparticles. Unlike BiVO₄, Nd-doped LuPO₄ NPs are highly crystalline as-prepared and do not require annealing, a time and energy-intensive step, simplifying the production.

We demonstrate that LuPO₄:Nd³⁺ NPs can be easily modified to achieve excellent colloidal stability while maintaining bright luminescence, detectable in vivo using non-ionizing excitation wavelengths and fluorescence microscopy. Additionally, we compared results from inductively coupled plasma mass spectrometry (ICP-MS), a standard technique for element quantification, with those obtained using a highly sensitive superconducting nanowire single-photon detector (SNSPD) to accurately measure how the NPs distribute into different key organs.
In conclusion, Nd³⁺-doped LuPO₄ NPs show great promise as bioimaging agents for in vivo applications, with potential theranostic uses in diseases such as pneumonia, cancer, and Alzheimer's disease.