ABSTRACT
Developments in the design of lanthanide oxide nanoparticles (NPs) have unleashed a wide variety of biomedical applications. Several types of hepatic cancer cells overexpress two proteins: the gastrin-releasing peptide receptor (GRPr), which specifically recognizes the bombesin (BN) peptide, and the prostate-specific membrane antigen (PSMA), which specifically binds to several peptides that inhibit its activity (iPSMA). This research synthesized and physicochemically characterized Sm2O3 nanoparticles functionalized with the iPSMA-BN heterodimeric peptide and studied the effects on their structural, biochemical and preclinical properties after activation by neutron irradiation for possible use in molecular dual-targeted radiotherapy of hepatocellular carcinoma. The Sm2O3 NPs were synthesized by the precipitation-calcination method and functionalized with iPSMA-BN peptide using the DOTA macrocycle as a linking agent. Analysis of physicochemical characterization via TEM, EDS, XRD, UV-Vis, FT-IR, DSL, and zeta potential results showed the formation of Sm2O3-iPSMA-BN NPs (94.23 ± 5.98 nm), and their physicochemical properties were not affected after neutron activation. The nanosystem showed a high affinity with respect to PSMA and GRPr in HepG2 cells ( Kd = 6.6 ± 1.6 nM) and GRPr in PC3 cells ( Kd = 10.6 ± 1.9 nM). 153Sm2O3-iPSMA-BN NPs exhibited radioluminescent properties, making possible in vivo optical imaging of their biodistribution in mice. The results obtained from this research support further preclinical studies designed to evaluate the dosimetry and therapeutic efficacy of 153Sm2O3-iPSMA-BN nanoparticles for in vivo imaging and molecular dual-targeted radiotherapy of liver tumors overexpressing PSMA and/or GRPr proteins.
Subject(s)
Metal Nanoparticles , Animals , Bombesin , Cell Line, Tumor , Humans , Mice , Oxides , Radioisotopes , Samarium , Spectroscopy, Fourier Transform Infrared , Tissue DistributionABSTRACT
The aim of this research was to evaluate the cell cycle redistribution and activation of early and late apoptotic pathways in lymphoma cells after treatment with 177Lu-anti-CD20. Experimental and computer models were used to calculate the radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo, PENELOPE) consisted of twenty spheres representing cells with an inner sphere (cell nucleus) embedded in culture media. Radiation emissions of the radiopharmaceutical located in cell membranes and in culture media were considered for nuclei dose calculations. Flow cytometric analyses demonstrated that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate late apoptotic pathways.
Subject(s)
Apoptosis/radiation effects , Lutetium/therapeutic use , Lymphoma/radiotherapy , Radioimmunotherapy/methods , Radioisotopes/therapeutic use , Rituximab/therapeutic use , Apoptosis/immunology , Cell Line, Tumor , Dose-Response Relationship, Radiation , Flow Cytometry , G2 Phase Cell Cycle Checkpoints/radiation effects , Humans , Immunoconjugates/therapeutic use , Lymphoma/immunology , Lymphoma/pathologyABSTRACT
The aim of this work was to evaluate the tumoral fibrosis effect on the radiation absorbed dose of the radiopharmaceuticals (177)Lu-Tyr(3)-octreotate (monomeric) and (177)Lu-Tyr(3)-octreotate-gold nanoparticles (multimeric) using an experimental HeLa cells tumoral model and the Monte Carlo PENELOPE code. Experimental and computer micro-environment models with or without fibrosis were constructed. Results showed that fibrosis increases up to 33% the tumor radiation absorbed dose, although the major effect on the dose was produced by the type of radiopharmaceutical (112Gy-multimeric vs. 43Gy-monomeric).
Subject(s)
Lutetium/administration & dosage , Neoplasms/pathology , Neoplasms/radiotherapy , Octreotide/analogs & derivatives , Radioisotopes/administration & dosage , Radiopharmaceuticals/administration & dosage , Fibrosis , Gold , HeLa Cells , Humans , Lutetium/chemistry , Lutetium/pharmacokinetics , Metal Nanoparticles/administration & dosage , Metal Nanoparticles/chemistry , Models, Biological , Monte Carlo Method , Neoplasms/metabolism , Octreotide/administration & dosage , Octreotide/chemistry , Octreotide/pharmacokinetics , Radioisotopes/chemistry , Radioisotopes/pharmacokinetics , Radiopharmaceuticals/chemistry , Radiopharmaceuticals/pharmacokinetics , Radiotherapy Dosage , Theranostic NanomedicineABSTRACT
Nanoparticles can be near infrared (NIR)-fluorescent (e.g., gold nanoparticles, quantum dots or carbon nanotubes) or can have magnetic properties (e.g., iron oxide nanoparticles). These optical or magnetic properties can be exploited for use in thermal therapy and molecular imaging. Radiolabeled nanoparticles have proven to be promising tools in the diagnosis and therapy of malignant processes due to their multivalency and as multi-modal imaging agents. Furthermore, these radiopharmaceuticals may function simultaneously as both radiotherapy systems and thermal-ablation systems. This review examines the application of radiolabeled nanoparticles in the development of multifunctional nanosystems for targeted therapy.
