| Summary: | Rare-earth nanomaterials are being widely applied in medicine as cytotoxicity agents, in radiation and photodynamic therapy, as drug carriers, and in biosensing and bioimaging technology. Terbium (Tb), a rare-earth element belonging to the lanthanides, has a long luminescent lifetime, large stock displacement, narrow spectral width, and biofriendly probes. In cancer therapy, cancer stem cell (CSC)-targeted treatment is receiving considerable attention due to these cells’ harmful characteristics. However, CSCs remain barely understood. Therefore, to effectively label and inhibit the growth of CSCs, we produced a nanocomplex in which TbPO<sub>4</sub>·H<sub>2</sub>O nanorods were double conjugated with CD133 and PD-L1 monoclonal antibodies. The Tb<sup>3+</sup> nanomaterials were created in the presence of a soft template (polyethylene glycol 2000). The obtained nanomaterial TbPO<sub>4</sub>·H<sub>2</sub>O was hexagonal crystal and nanorod in shape, 40−80 nm in diameter, and 300−800 nm in length. The nanorods were further surfaced through tetraethyl orthosilicate hydrolysis and functionalized with amino silane. Finally, the glutaraldehyde-activated Tb<sup>3+</sup> nanorods were conjugated with CD133 monoclonal antibody and PD-L1 monoclonal antibody on the surface to obtain the nanocomplex TbPO<sub>4</sub>·H<sub>2</sub>O@silica-NH<sub>2</sub>+mAb^CD133+mAb^PD-L1 (<b>TMC</b>). The formed nanocomplex was able to efficiently and specifically label NTERA-2 cells, a highly expressed CD133 and PD-L1 CSC cell line. The conjugate also demonstrated promising anti-CSC activity by significant inhibition (58.50%) of the growth of 3D tumor spheres of NTERA-2 cells (<i>p</i> < 0.05).
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