RESUMO
The synthesis of core-shell star copolymers via living free radical polymerization provides a convenient route to three-dimensional nanostructures having a poly(ethylene glycol) outer shell, a hydrophilic inner shell bearing reactive functional groups, and a central hydrophobic core. By starting with well-defined linear diblock copolymers, the thickness of each layer, overall size/molecular weight, and the number of internal reactive functional groups can be controlled accurately, permitting detailed structure/performance information to be obtained. Functionalization of these polymeric nanoparticles with a DOTA-ligand capable of chelating radioactive (64)Cu nuclei enabled the biodistribution and in vivo positron emission tomography (PET) imaging of these materials to be studied and correlated directly to the initial structure. Results indicate that nanoparticles with increasing PEG shell thickness show increased blood circulation and low accumulation in excretory organs, suggesting application as in vivo carriers for imaging, targeting, and therapeutic groups.
Assuntos
Compostos Heterocíclicos com 1 Anel/metabolismo , Polietilenoglicóis/química , Polímeros/química , Polímeros/síntese química , Tomografia por Emissão de Pósitrons , Animais , Radioisótopos de Cobre , Portadores de Fármacos , Feminino , Espectroscopia de Ressonância Magnética , Nanopartículas , Polímeros/metabolismo , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Distribuição TecidualRESUMO
The synthesis of poly(methyl methacrylate-co-methacryloxysuccinimide-graft-poly(ethylene glycol)) (PMMA-co-PMASI-g-PEG) via living free radical polymerization provides a convenient route to well-defined amphiphilic graft copolymers having a controllable number of reactive functional groups, variable length PEG grafts, and low polydispersity. These copolymers were shown to form PMMA-core/PEG-shell nanoparticles upon hydrophobic collapse in water, with the hydrodynamic size being defined by the molecular weight of the backbone and the PEG grafts. Functionalization of these polymeric nanoparticles with a 1,4,7,10-tetraazacyclododecanetetraacetic acid (DOTA) ligand capable of chelating radioactive 64Cu nuclei enabled the biodistribution and in vivo positron emission tomography of these materials to be studied and directly correlated to the initial structure. Results indicate that nanoparticles with increasing PEG chain lengths show increased blood circulation and low accumulation in excretory organs, suggesting the possible use of these materials as stealth carriers for medical imaging and systemic administration.
Assuntos
Radioisótopos de Cobre/farmacocinética , Nanopartículas/química , Tomografia por Emissão de Pósitrons/instrumentação , Tomografia por Emissão de Pósitrons/métodos , Animais , Materiais Biocompatíveis/química , Cobre/química , Radioisótopos de Cobre/química , Microscopia Crioeletrônica , Feminino , Radicais Livres , Ligantes , Metacrilatos/química , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Polietilenoglicóis/química , Polimetil Metacrilato/química , Ratos , Ratos Sprague-DawleyRESUMO
Radiolabeling studies were employed to investigate the influence of structure on the efficiency of surface functionalization for poly(acrylic acid)-coated shell crosslinked nanoparticles (SCKs) with two types of amine-terminated DOTA chelators. An intricate interplay between the chemical and physical properties of both the DOTA derivative and the SCK nanostructures was revealed, demonstrating the importance of structural control.
