Synthesis, characterization and radiolabeling of polymeric nano-micelles as a platform for tumor delivering

• Published in: Biomedicine & pharmacotherapy Vol. 89; pp. 268 - 275
• Main Authors: Oda, Caroline Mari Ramos, Fernandes, Renata Salgado, de Araújo Lopes, Sávia Caldeira, de Oliveira, Mônica Cristina, Cardoso, Valbert Nascimento, Santos, Daniel Moreira, de Castro Pimenta, Adriano Monteiro, Malachias, Angelo, Paniago, Rogério, Townsend, Danyelle M, Colletti, Patrick M, Rubello, Domenico, Alves, Ricardo José, de Barros, André Luís Branco, Leite, Elaine Amaral
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.05.2017
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Characterization; Drug Delivery Systems - methods; Internal Medicine; Medical Education; Mice; Mice, Inbred BALB C; Micelles; Nanoparticles - chemistry; Neoplasms - drug therapy; Platform for tumor delivering; Polyethylene Glycols - chemistry; Polymeric micelles; Polymers - chemistry; Radioisotopes - chemistry; Radiolabeling; Synthesis; Tissue Distribution - physiology; Characterization; Radiolabeling; Synthesis; Polymeric micelles; Platform for tumor delivering
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.01.144

Abstract The use of nanoparticles for diagnostic approaches leads to higher accumulation in the targeting tissue promoting a better signal-to-noise ratio and consequently, early tumor detection through scintigraphic techniques. Such approaches have inherent advantages, including the possibility of association with a variety of gamma-emitting radionuclides available, among them, Tecnethium–99 m (99m Tc).99m Tc is readily conjugated with nanoparticles using chelating agents, such as diethylenetriaminepentaacetic acid (DTPA). Leveraging this approach, we synthesized polymeric micelles (PM) consisting of 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -[methoxy(polyethyleneglycol)-2000] (DSPE-mPEG2000 ) functionalized with DTPA for radiolabeling with99m Tc. Micelles made up of DSPE-mPEG2000 and DSPE-PEG2000 -DTPA had a mean diameter of  ∼10 nm, as measured by DLS and SAXS techniques, and a zeta potential of −2.7 ± 1.1 mV. Radiolabeled micelles exhibited high radiochemical yields and stability. In vivo assays indicated long blood circulation time (456.3 min). High uptake in liver, spleen and kidneys was observed in the biodistribution and imaging studies on healthy and tumor-bearing mice. In addition, a high tumor-to-muscle ratio was detected, which increased over time, showing accumulation of the PM in the tumor region. These findings indicate that this system is a promising platform for simultaneous delivery of therapeutic agents and diagnostic probes.