Li-Doped NaYF<sub>4</sub>:Ho,Yb Upconversion Nanoparticles for Chemotherapy and Radionuclide Therapy of Cancer
Ruchi Agrawal, Sourav Patra, Sandeep B. Shelar, Chandan Kumar, Manas Srivastava, Sudipta Chakraborty, R. S. Ningthoujam
Abstract
Highly luminescent, biocompatible, and water-dispersible monodispersed NaYF 4:Ho,Yb,Li (YHYL) upconversion nanoparticles (NPs) entrapped into mesoporous silica (YHYL@m-SiO 2 ) have been prepared. The surface area of YHYL@m-SiO 2 NPs is found to be 128 m 2 /g with pore sizes of 3–4 nm. To illustrate the use of these YHYL@m-SiO 2 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-SiO 2 -NH 2 -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-SiO 2 -NH 2 -FA-DOX NPs) in targeted radionuclide therapy, these NPs are radiolabeled with 177 Lu, a β – -emitting radionuclide [ T 1/2 = 6.65 d, E β (max) = 497 keV, E γ = 113 keV (6.4%), 208 keV (11%)] extensively used for targeted radionuclide therapy. It is experimentally established that the adsorption of 177 Lu on YHYL@m-SiO 2 -NH 2 -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 [ 177 Lu]Lu-YHYL@m-SiO 2 -NH 2 -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-SiO 2, YHYL@m-SiO 2 -DOX, YHYL@m-SiO 2 -NH 2 -FA-DOX and [ 177 Lu]Lu-YHYL@m-SiO 2 -NH 2 -FA-DOX NPs, their physicochemical characterization, and their potential applications in combination cancer therapy have been amply demonstrated.