RESUMO
The prostate specific membrane antigen (PSMA) is broadly overexpressed on prostate cancer (PCa) cell surfaces. In this study, we report the synthesis, characterization, in vitro binding assay, and in vivo magnetic resonance imaging (MRI) evaluation of PSMA targeting superparamagnetic iron oxide nanoparticles (SPIONs). PSMA-targeting polypeptide CQKHHNYLC was conjugated to SPIONs to form PSMA-targeting molecular MRI contrast agents. In vitro studies demonstrated specific uptake of polypeptide-SPIONs by PSMA expressing cells. In vivo MRI studies found that MRI signals in PSMA-expressing tumors could be specifically enhanced with polypeptide-SPION, and further Prussian blue staining showed heterogeneous deposition of SPIONs in the tumor tissues. Taken altogether, we have developed PSMA-targeting polypeptide-SPIONs that could specifically enhance MRI signal in tumor-bearing mice, which might provide a new strategy for the molecular imaging of PCa.
Assuntos
Antígenos de Superfície/química , Compostos Férricos/química , Glutamato Carboxipeptidase II/química , Nanopartículas Metálicas/química , Neoplasias da Próstata/diagnóstico , Animais , Linhagem Celular Tumoral , Meios de Contraste/química , Ferrocianetos/química , Humanos , Ácido Láctico/química , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Nanotecnologia , Transplante de Neoplasias , Peptídeos/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Neoplasias da Próstata/patologia , Ligação Proteica , Transdução de SinaisRESUMO
Magnetite loaded Polypeptide-PLGA multifunctional microbubbles (Fe3O4 /Polypeptide-PLGA MMBs) that show superparamagnetic properties were prepared by a modified double emulsion method and employed as imaging agent for dual-mode Ultrasound/Magnetic resonance (US/MR) imaging of prostatic cancer. The successful synthesis of MMBs was determined by Fourier Transform Infrared Spectrometer (FTIR), X-ray diffraction (XRD), Transmission Electron Microscope (TEM), Scanning Electron Microscope (SEM), Atomic Absorption Spectroscopy (AAS) and vibrating sample magnetometer (VSM). The as-prepared MMBs had a diameter of 700 nm and were quite safe as confirmed by MTT assays. Prussian Blue Staining showed that targeted Fe3O4 /Polypeptide-PLGA MMBs enhanced the cellular uptake efficiency. In cell attachment study, adherence of MMBs was significantly higher to LNCaP cells compared with negative control PC3 cells. The in vitro results demonstrated that these MMBs could enhance both US and MR imaging of prostatic cancer.