WMO Education and Training Programme

Biomedical Imaging Applications of Lanthanide-doped Upconverting Nanoparticles

Deep tissue imaging

Near-infrared excitation (such as 808 nm or 975 nm) significantly increases the penetration depth to the millimeter level by reducing light scattering and absorption in biological tissues. For example, Tm³⁺/Yb³⁺-doped sodium fluoride nanocrystals (20-30 nm) can emit ~800 nm near-infrared light under 975 nm excitation, achieving high-contrast imaging in mice without significant cytotoxicity. CaF₂:Tm,Yb nanoparticles have a penetration depth of nearly 2 mm at low power density, while the core-shell structure (α-NaYbF₄:Tm)@CaF₂ can even penetrate 16 mm of muscle and bone tissue, providing a technical basis for single-particle analysis of tumor microenvironment heterogeneity. In addition, by exciting UCNPs with a 980 nm annular beam and combining nonlinear saturated emission characteristics, 60 nm super-resolution imaging (NIRES nano-imaging technology) can be achieved in deep tissues, significantly improving the accuracy of tumor boundary identification.

Multimodal imaging

Upconverting nanoparticles (UCNPs) can integrate multiple imaging modes by doping or compounding functional components. For example, the NaGdF₄:Yb,Er@NaGdF₄ core-shell structure combines Upconverting luminescence (UCL) and T1-weighted magnetic resonance imaging (MRI) functions, and its longitudinal relaxation rate (r₁) reaches 5.60 s⁻¹·mM⁻¹, which is better than clinical gadolinium-based contrast agents. Similarly, 18F-labeled NaYF₄:Yb,Er,Gd nanoparticles can simultaneously support positron emission tomography (PET), MRI, and UCL imaging, achieving multi-scale diagnosis from cells to living bodies, with complementary advantages in sensitivity and spatial resolution. This multimodal design not only improves diagnostic accuracy, but also allows real-time monitoring of dynamic changes in tumors during treatment, such as synchronous imaging of cell apoptosis during the release of photoactivated platinum prodrugs.

UCNPs can convert near-infrared light into ultraviolet/visible light, activating photosensitizers (such as Ce6) to produce reactive oxygen species (ROS). For example, NaYF₄:Yb,Tm@SiO₂ nanoparticles emit 365 nm ultraviolet light under 980 nm excitation to trigger zinc phthalocyanine (ZnPc) to generate singlet oxygen, and the apoptosis induction efficiency of drug-resistant ovarian cancer cells is 80%. To enhance the photothermal conversion efficiency, the Au@UCNPs core-shell structure can be heated to 50°C under 4 W/cm² laser to directly kill cancer cells, while the surface plasmon resonance effect of the gold shell is used to enhance near-infrared absorption.

Chemotherapeutic drugs (such as gemcitabine) can be loaded by coating UCNPs with mesoporous silica or polydopamine. Near-infrared light-triggered drug release increases the local concentration of tumors by 3-5 times, while significantly reducing systemic toxicity. For example, folic acid-modified UCNPs can target tumor cells with high expression of folate receptors, and combine MRI/UCL dual-mode imaging to track drug distribution in real time. In addition, pH-responsive coatings (such as polyethylene glycol-polylactic acid) can selectively release doxorubicin in the slightly acidic environment of tumors to enhance therapeutic specificity.

Integration of Diagnosis and Treatment and Clinical Transformation

UCNPs can be used as both imaging probes and therapeutic carriers. In a pancreatic cancer model, UCNPs targeting EGFR combined with photodynamic therapy (PDT) reduced tumor volume by 70% and prolonged mouse survival by 2 times. The latest preclinical studies showed that intraoperative real-time imaging can accurately guide tumor resection boundaries (error < 0.5 mm), and simultaneously implement PDT to reduce postoperative recurrence. In addition, 18F-labeled UCNPs can dynamically evaluate drug metabolism and efficacy through PET/MRI multimodal imaging, providing a basis for personalized treatment.

Lanthanide-doped Upconverting nanoparticles are reshaping the technical boundaries of biomedical imaging and treatment with their unique optical properties and programmable functions. In the future, through intelligent response design (such as pH or enzyme triggering) and clinical transformation optimization, UCNPs are expected to become one of the core tools of precision medicine.