RESUMO
Ewing's sarcoma is a rare, mostly pediatric bone cancer that presents a chromosome abnormality called EWS/Fli-1, responsible for the development of the tumor. In vivo, tumor growth can be inhibited specifically by delivering small interfering RNA (siRNA) associated with nanoparticles. The aim of the work was to design targeted nanoparticles against the cell membrane glycoprotein cd99, which is overexpressed in Ewing's sarcoma cells to improve siRNA delivery to tumor cells. Biotinylated poly(isobutylcyanoacrylate) nanoparticles were conceived as a platform to design targeted nanoparticles with biotinylated ligands and using the biotin-streptavidin coupling method. The targeted nanoparticles were validated in vivo for the targeted delivery of siRNA after systemic administration to mice bearing a tumor model of the Ewing's sarcoma. The expression of the gene responsible of Ewing's sarcoma was inhibited at 78% ± 6% by associating the siRNA with the cd99-targeted nanoparticles compared with an inhibition of only 41% ± 9% achieved with the nontargeted nanoparticles.
Assuntos
Antígenos CD/genética , Moléculas de Adesão Celular/genética , Nanopartículas/química , RNA Interferente Pequeno/administração & dosagem , Sarcoma de Ewing/metabolismo , Sarcoma de Ewing/terapia , Antígeno 12E7 , Animais , Moléculas de Adesão Celular/antagonistas & inibidores , Quitosana/química , Humanos , Camundongos , Camundongos Nus , Microscopia Eletrônica de Transmissão , Nanopartículas/administração & dosagem , Nanopartículas/ultraestrutura , Polímeros/química , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/fisiologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The success of the application of new therapeutic methods based on RNA interfering strategies requires the in vivo delivery of active ODN or siRNA down to the intracellular compartment of the target cells. This article aims to review the studies related to the formulation of RNA interfering agents in polymer nanocarriers. It will present the different types of polymer nanocarriers used as well as the biological activity of the resulting ODN and siRNA loaded nanocarriers. As will be explained, the part of the in vitro studies provided useful data about the intracellular delivery of the formulated RNA interfering agents. Investigations performed in vivo have considered animal models of different relevant diseases. Results from these investigations have clearly demonstrated the interest of several polymer nanocarriers tested so far to deliver active RNA interfering effectors in vivo making possible their administration by the intravenous route.
