The detection of lymph node metastasis is of great importance for therapy planning and prognosis of cancers, but remains challenging in the clinic. In the current study, we report a tumor-specific imaging probe constructed with NaGdF₄:Yb,Tm,Ca@NaLuF₄ core@shell upconversion nanoparticles showing distinctive near infrared emission. The following studies revealed that the characteristic Tm dopant emission at 804 nm showed a penetration depth up to 7.7 mm through multi-layered mice skin tissues, substantially greater than emissions at 655 nm and 541 nm typically from the widely used Er dopant, which is apparently favorable for sensitive tumor diagnosis. The cell binding assay further revealed that the anti-HER2 antibodies covalently attached on the particle surface endowed the nanoprobe with excellent binding specificity in targeting HER2-positive cancer cells in vitro, which further enabled the detection of lymph node metastasis of breast cancer in vivo in mice. In addition, the pharmacokinetics of the resulting nanoprobes were intensively studied through both upconversion luminescence imaging and SPECT imaging for comparing with that of the mother particles. The results obtained through both approaches were well consistent and revealed that the surface conjugation of antibodies largely altered the pharmacokinetic behaviors and substantially prolonged the blood half-life of the underlying nanoparticles, which was never reported before.

Background: Pancreatic ductal adenocarcinoma (PDAC) is a devastatingly malignant tumor with a high mortality. However, current strategies to treat PDAC generally have low efficacy and high side-effects, therefore, effective treatment against PDAC remains an urgent need. Results: We report a semiconducting polymer nano-radiopharmaceutical with intrinsic photothermal capability and labeling with therapeutic radioisotope ¹⁷⁷Lu (¹⁷⁷Lu-SPN-GIP) for combined radio- and photothermal therapy of pancreatic tumor. ¹⁷⁷Lu-SPN-GIP endowed good stability at physiological conditions, high cell uptake, and long retention time in tumor site. By virtue of combined radiotherapy (RT) and photothermal therapy (PTT), ¹⁷⁷Lu-SPN-GIP exhibited enhanced therapeutic capability to kill cancer cells and xenograft tumor in living mice compared with RT or PTT alone. More importantly, ¹⁷⁷Lu-SPN-GIP could suppress the growth of the tumor stem cells and reverse epithelial mesenchymal transition (EMT), which may greatly reduce the occurrence of metastasis. Conclusion: Such strategy we developed could improve therapeutic outcomes over traditional RT as it is able to ablate tumor with relatively lower doses of radiopharmaceuticals to reduce its side effects. Graphical

This paper presents a comprehensive review of recent advancements in radionuclide-labeled biomaterials for cancer therapy, with a particular focus on the characteristics, production methods, and labeling techniques of α-particle, β-particle, and Auger electron-based radiotherapy. It explores innovative strategies for targeted delivery systems and highlights the advantages of theranostics and combination therapies. The application of radionuclide-labeled biomaterials in various cancer types, including prostate cancer, breast cancer, neuroendocrine tumors, gliomas, and melanoma, is systematically summarized. Furthermore, the article critically examines current technological bottlenecks and challenges in clinical translation, while proposing future directions such as AI-assisted dose optimization and multimodal combination therapies. This review provides essential theoretical foundations and practical insights to facilitate the clinical translation of radionuclide-labeled biomaterials.