Li-Doped NaYF₄:Ho,Yb Upconversion Nanoparticles for Chemotherapy and Radionuclide Therapy of Cancer

Highly luminescent, biocompatible, and water-dispersible monodispersed NaYF4:Ho,Yb,Li (YHYL) upconversion nanoparticles (NPs) entrapped into mesoporous silica (YHYL@m-SiO2) have been prepared. The surface area of YHYL@m-SiO2 NPs is found to be 128 m2/g with pore sizes of 3–4 nm. To illustrate the use of these YHYL@m-SiO2 NPs as drug (DOX) carriers, an in-depth analysis is conducted. In order to use these nanoparticles for targeted cancer therapy, folic acid (FA) is also chemically conjugated to them. The affinity of YHYL@m-SiO2-NH2-FA-DOX NPs with folate receptors (FRs) are proved by in vitro studies. To demonstrate the potential utility of DOX-loaded and folic acid–conjugated nanoparticles (YHYL@m-SiO2-NH2-FA-DOX NPs) in targeted radionuclide therapy, these NPs are radiolabeled with 177Lu, a β–-emitting radionuclide [T1/2= 6.65 d, Eβ(max) = 497 keV, Eγ = 113 keV (6.4%), 208 keV (11%)] extensively used for targeted radionuclide therapy. It is experimentally established that the adsorption of 177Lu on YHYL@m-SiO2-NH2-FA-DOX NPs follows a combination of Langmuir and Freundlich isotherm models and pseudo-second-order kinetics. Cell toxicity and apoptotic cell death studies are conducted for [177Lu]Lu-YHYL@m-SiO2-NH2-FA-DOX NPs in the MCF-7 cell line, which demonstrated the therapeutic potential of the radiolabeled and drug-loaded formulation in an in vitro model. Overall, the syntheses of YHYL@m-SiO2, YHYL@m-SiO2-DOX, YHYL@m-SiO2-NH2-FA-DOX and [177Lu]Lu-YHYL@m-SiO2-NH2-FA-DOX NPs, their physicochemical characterization, and their potential applications in combination cancer therapy have been amply demonstrated.