Cancer Stem Cell Target Labeling and Efficient Growth Inhibition of CD133 and PD-L1 Monoclonal Antibodies Double Conjugated with Luminescent Rare-Earth Tb3+ Nanorods

Abstract

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 TbPO4·H2O nanorods were double conjugated with CD133 and PD-L1 monoclonal antibodies. The Tb3+ nanomaterials were created in the presence of a soft template (polyethylene glycol 2000). The obtained nanomaterial TbPO4·H2O 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 Tb3+ nanorods were conjugated with CD133 monoclonal antibody and PD-L1 monoclonal antibody on the surface to obtain the nanocomplex TbPO4·H2O@silica-NH2+mAb^CD133+mAb^PD-L1 (TMC). 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 (p < 0.05).