Nearly monodispersed NaGdF4/Ho–Yb upconversion nanoparticles (UCNPs) are synthesized by thermolysis of respective rare earth oleates. UCNPs are made biocompatible by mesoporous silica (m-SiO2) coating. These particles exhibit red and green bands in the visible range upon excitation at 980 nm laser. Interestingly, because of the presence of Ho3+ ions, these UCNPs can be excited via UV–vis light in addition to the 980 nm near infrared light. A systematic study is carried out to demonstrate the use of these UCNPs as drug (DOX) carriers. Toxicity studies and bio-imaging using DOX-loaded UCNPs have been demonstrated. UCNPs are also radiolabeled with 177Lu using m-SiO2 coating to demonstrate its potential application as a carrier of the therapeutic radionuclide in vivo for radionuclide therapy. Lu-177 adsorption studies are carried out extensively in order to understand the nature of adsorption, and it is found to be a combination of Langmuir and Freundlich isotherm models. Kinetics of adsorption of Lu3+ ions on the m-SiO2 coating of UCNPs is studied. Overall, the synthesis and physicochemical characterization of NaGdF4/Ho–Yb@m-SiO2 upconversion nanocrystals and their potential utilities in multimodal biomedical applications are amply demonstrated.

Biomimetic hydroxyapatite nanoparticles (HAnps) are among the few nanostructured materials used clinically as potential carriers of drugs and biomolecules. Moreover, they have strong affinity toward lanthanide cations (such as Sm+3, Lu+3, Ho+3, etc.), which provides the scope for robust chelator-free radiolabeling with suitable lanthanide radioisotopes. Therefore, this nanoplatform can be used as a carrier of a cytotoxic payload of therapeutic radioisotopes. In the present study, HAnps were synthesized by the sol–gel method and functionalized with sodium citrate to impart water dispersibility. The synthesized nanoparticles were characterized using various analytical techniques. The particle size of the citrate-functionalized hydroxyapatite nanoparticles (Cit-HAnps) was found to be 205 ± 7 nm. A chelator-free method to radiolabel the Cit-HAnp with 177Lu [T 1/2 = 6.65 days, E β(max) = 497 keV, E γ = 113 (6.4%) and 208 keV (11.0%)] was optimized to get the 177Lu-labeled nanoformulation with >98% radiochemical purity. The adsorption-based radiolabeling method followed the Langmuir isotherm and pseudo-second-order kinetic model, indicating that the process was chemisorption. In vitro bone binding and cell toxicity study established the therapeutic efficacy of the radiolabeled nanoparticles. SPECT/CT imaging in healthy Wistar rats after administration of the radiolabeled nanoparticles was performed to demonstrate the in vivo stability and clearance pattern. Density functional theory (DFT) calculations were performed to provide the structural modification of Cit-HAnps and a glimpse into the probable mechanism of chelator-free labeling of 177Lu on Cit-HAnps. Overall, this class of nanomaterials provides an avenue toward the development of clinically translatable radionanomedicine for use in cancer theranostics.

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