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Upconversion nanoplatform unlocks the theranostic potential of Lu-177 radiotherapy via c-MET axis targeting in head and neck squamous cell carcinoma.

Created on 06 Sep 2026

Authors

Kai-Hung Lin, Chun-Yi Wu, Yu-Chan Chang, Ming-Hsien Chan

Published in

Materials today. Bio. Volume 40. Pages 103585. Epub Aug 25, 2026.

Abstract

Upconversion nanoparticles (UCNPs) convert tissue-penetrating near-infrared photons into sharp visible emissions, offering background-free optical readouts for deep-tissue imaging. Here we report multilayer NaLuF4:Yb,Tm@NaLuF4 UCNPs that simultaneously act as fluorescent probes and radioisotope precursors. Under 980 nm excitation, the particles generate bright blue and red upconversion signals for real-time tracking. At the same time, their lutetium-rich core can be neutron-activated in a single step to yield β-- and γ-emitting 177Lu. The β-particles confine cytotoxic dose within a 2 mm range, whereas the co-emitted γ photons enable quantitative single-photon emission computed tomography (SPECT). To enhance the tumor selectivity of the nanoplatform, we grafted a c-Met DNA aptamer onto the PEGylated shell, guiding the nanoconstructs to target head and neck squamous cell carcinoma (HNSCC) with amplified c-Met receptor levels. The aptamer markedly enhances cellular uptake, improves therapeutic indices, and limits off-target irradiation. Moreover, the optical modality remains non-radioactive, allowing pre-treatment imaging without patient exposure, and supplements the relatively low (∼10%) γ yield of 177Lu for accurate intra-procedural localization. Collectively, this single nanosystem unites targeted radiotherapy, radionuclide therapy, SPECT, and NIR-mediated optical imaging, delivering a coherent "see-and-treat" strategy for HNSCC. The modular design also provides a versatile platform that can be transferred to other solid tumors bearing actionable biomarkers across diverse clinical oncology imaging and therapy settings.

PMID:
42701510
Bibliographic data and abstract were imported from PubMed on 06 Sep 2026.

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