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

Publication date: May 2017
Source:Biomedicine & Pharmacotherapy, Volume 89
Author(s): Caroline Mari Ramos Oda, Renata Salgado Fernandes, Sávia Caldeira de Araújo Lopes, Mônica Cristina de Oliveira, Valbert Nascimento Cardoso, Daniel Moreira Santos, Adriano Monteiro de Castro Pimenta, Angelo Malachias, Rogério Paniago, Danyelle M. Townsend, Patrick M. Colletti, Domenico Rubello, Ricardo José Alves, André Luís Branco de Barros, Elaine Amaral Leite
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–99m (^99mTc). ^99mTc 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 with ^99mTc. Micelles made up of DSPE-mPEG2000 and DSPE-PEG2000-DTPA had a mean diameter of  ∼10nm, as measured by DLS and SAXS techniques, and a zeta potential of −2.7±1.1mV. Radiolabeled micelles exhibited high radiochemical yields and stability. In vivo assays indicated long blood circulation time (456.3min). 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.



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