Chelator-Free Radiolabeling with Theoretical Insights and Preclinical Evaluation of Citrate-Functionalized Hydroxyapatite Nanospheres for Potential Use as Radionanomedicine

• Published in: Industrial & engineering chemistry research Vol. 62; no. 7; pp. 3194 - 3205
• Main Authors: Patra, Sourav, Kancharlapalli, Srinivasu, Chakraborty, Avik, Singh, Khajan, Kumar, Chandan, Guleria, Apurav, Rakshit, Sutapa, Damle, Archana, Chakravarty, Rubel, Chakraborty, Sudipta
• Format: Journal Article
• Language: English
• Published: American Chemical Society 22.02.2023
• Subjects: Materials and Interfaces
• ISSN: 0888-5885; 1520-5045
• DOI: 10.1021/acs.iecr.2c04378

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.