Li-Doped NaYF<sub>4</sub>:Ho,Yb Upconversion Nanoparticles\nfor Chemotherapy and Radionuclide Therapy of Cancer

Highly luminescent, biocompatible,\nand water-dispersible\nmonodispersed\nNaYF<sub>4</sub>:Ho,Yb,Li (YHYL) upconversion nanoparticles (NPs)\nentrapped into mesoporous silica (YHYL@m-SiO<sub>2</sub>) have been\nprepared. The surface area of YHYL@m-SiO<sub>2</sub> NPs is found\nto be 128 m<sup>2</sup>/g with pore sizes of 3–4 nm. To illustrate\nthe use of these YHYL@m-SiO<sub>2</sub> NPs as drug (DOX) carriers,\nan in-depth analysis is conducted. In order to use these nanoparticles\nfor targeted cancer therapy, folic acid (FA) is also chemically conjugated\nto them. The affinity of YHYL@m-SiO<sub>2</sub>-NH<sub>2</sub>-FA-DOX\nNPs with folate receptors (FRs) are proved by <i>in vitro</i> studies. To demonstrate the potential utility of DOX-loaded and\nfolic acid–conjugated nanoparticles (YHYL@m-SiO<sub>2</sub>-NH<sub>2</sub>-FA-DOX NPs) in targeted radionuclide therapy, these\nNPs are radiolabeled with <sup>177</sup>Lu, a β<sup>–</sup>-emitting radionuclide [<i>T</i><sub>1/2</sub>= 6.65 d, <i>E</i><sub>β</sub>(max) = 497 keV, <i>E</i><sub>γ</sub> = 113 keV (6.4%), 208 keV (11%)] extensively used for\ntargeted radionuclide therapy. It is experimentally established that\nthe adsorption of <sup>177</sup>Lu on YHYL@m-SiO<sub>2</sub>-NH<sub>2</sub>-FA-DOX NPs follows a combination of Langmuir and Freundlich\nisotherm models and pseudo-second-order kinetics. Cell toxicity and\napoptotic cell death studies are conducted for [<sup>177</sup>Lu]Lu-YHYL@m-SiO<sub>2</sub>-NH<sub>2</sub>-FA-DOX NPs in the MCF-7 cell line, which demonstrated\nthe therapeutic potential of the radiolabeled and drug-loaded formulation\nin an <i>in vitro</i> model. Overall, the syntheses of YHYL@m-SiO<sub>2</sub>, YHYL@m-SiO<sub>2</sub>-DOX, YHYL@m-SiO<sub>2</sub>-NH<sub>2</sub>-FA-DOX and [<sup>177</sup>Lu]Lu-YHYL@m-SiO<sub>2</sub>-NH<sub>2</sub>-FA-DOX NPs, their physicochemical characterization, and their\npotential applications in combination cancer therapy have been amply\ndemonstrated.