Project objectives
The main objective of the project is in vitro and in vivo evaluation of anti-PSMA-functionalized NaA nanozeolites labeled with the alpha-emitter 223Ra as a new radio-immunoconjugate for targeted therapy of prostate cancer.
This will be achieved by pursuing the following sub-goals:
Synthesis and physicochemical characterization of anti-PSMA-functionalized NaA nanozeolites labeled with the alpha-emitter 223Ra.
Analysis of in vitro toxicity of unlabeled anti-PSMA-functionalized NaA nanozeolites and NaA nanozeolites as carriers with emphasis on cytotoxicity, inflammation and oxidative stress in human prostate cancer cells and normal prostate cells.
Assessment of in vitro efficacy of anti-PSMA-functionalized NaA nanozeolites labeled with the alpha-emitter 223Ra and NaA nanozeolites labeled with the alpha-emitter 223Ra with emphasis on binding affinity to PSMA receptors, ability to inhibit migration/invasion of prostate cancer cells and induction of DNA double strand breaks.
Preclinical pharmacokinetics and toxicity studies of NaA nanozeolite functionalized with anti-PSMA antibodies and labeled with barium-133 and radium-223 radioisotopes in normal mice.
Analysis of localization in vivo and biodistribution ex vivo of NaA nanozeolite functionalized with anti-PSMA antibodies and labeled with radium-223 and barium-133 radioizotope and NaA nanozeolite labeled with barium radioizotope as emitter of beta particles in murine model of human prostate cancer.