Design,Synthesis And Evaluation Of PSMA Targeted Super Paramagnetic Molecular Probe For Prostate Cancer

Prostate Cancer?PCa?is the most common malignant tumor of male genitourinary system,the early detection of cancer diseases is conducive to improving the cure rate and survival rate of cancer patients.Advances in science had promoted the progress of medical diagnosis.Medical imaging devices based on different principles,such as CT,PET/CT and MRI,are widely used in the diagnosis,treatment and tracking of diseases.The development of molecular imaging technology has further improved the level of medical diagnosis,the diagnosis of diseases has been upgraded from the pathological changes of organs,tissues and other macroscopical levels to the changes of cells and even molecules level.Therefore,selecting specific targets on cancer cells such as prostate cancer to develop a molecular imaging probe has important application value for the early diagnosis of prostate cancer and other cancers.PSMA,a transmembrane glycoprotein containing 750 amino acids,is highly expressed in prostate cancer epithelial cells.Currently,molecular imaging probes based on diagnostic molecular marker PSMA for prostate cancer include PET/CT molecular imaging probes labeled with ⁶⁸Ga and ^99mTc,optical imaging probes labeled with near infrared fluorescent dyes,and T1 and T2 MRI molecular imaging probes labeled with Gd3+,superparamagnetic iron oxide nanoparticles.Compared with Gd3+,ferric oxide nanoparticles have lower toxicity and better contrast effect.However,up to now,only PSMA antibody has been reported as a target molecule in the development of prostate cancer T2 imaging molecular probes based on ferric oxide nanoparticles,PSMA small molecule inhibitors with more latent application advantages have not been studied.Therefore,we designed and developed a novel molecular imaging probe Fe₃O₄@DPA-PEG-PSMA-1,PSMA as a specific target,Glu-Urea small molecule inhibitor as its target molecule,and T2 contrast agent Fe₃O₄ nanoparticles as tracer molecule.Fe₃O₄ nanoparticles were prepared by hydrothermal method.The synthesized Fe₃O₄nanoparticles were characterized by Fourier transform infrared spectroscopy?FT-IR?,transmission electron microscopy?TEM?,X-ray powder diffraction?XRD?and vibration magnetometer?VSM?,the characterization result proved that it was superparamagnetic Fe₃O₄ nanoparticles with a diameter of about 10 nm.PSMA-1 was synthesized based on L-glutamic acid and L-lysine with seven steps.The target product Fe₃O₄@DPA-PEG-PSMA-1 was synthesized by chemical bonding of Fe₃O₄ nanoparticles and PSMA-1 with polyethylene glycol 2000 polymer terminated with dopamine and amino group.Molecular probe Fe₃O₄@DPA-PEG-PSMA-1 was characterized by laser light scattering particle size analyzer and TEM.The results showed that it was well dispersed in aqueous solution with particle size ranging around 20 nm.Molecular probe Fe₃O₄@DPA-PEG-PSMA-1 could specifically bind to?PSMA+?LNcaP cells in vitro,but not to?PSMA-?HepG2 hepatoma cells.Further animal experiments showed that molecular probe Fe₃O₄@DPA-PEG-PSMA-1 could participate in the circulation in vivo and enrich on xenografted LNcaP cell tumors in nude mice after intravenous injection and up to the peak value after 3⁶h,There was almost nothing changed in Fe₃O₄@DPA-PEG-NH₂ negative control.The results of animal experiments were further supported by the section staining of tumors,Liver and Spleen issue.