The Targeted MR Imaging And Simultaneous Photothermal Therapy Of Prostate Cancer Using Multifunctional Theranostic Nanaoprobes USPION@Bn

Objective: To study the preparation and characterization of a multifunctional nanoprobe USPION@Bn by conjugating bombesin onto the surface of ultrasmall superparamagnetic iron-oxide nanoparticles and evaluate the application of this prepared nanoprobe in the field of magnetic molecular imaging and imaging-guided photothermal therapy(PTT) for prostate cancer(PCa).Methods:(1) Synthesize a multifunctional nanoprobe USPION@Bn by the covalent bioconjugation of USPION with Bn, and then properties were characterized.(2) The in vitro cytotoxicity is investigated via MTT assays. Then MR scanning and Calcein-AM/propidium iodide staining are performed to evaluate its in vitro targeting, imaging and photothermal ability.(3) After intravenous injection of USPION@Bn through the tail veins of PCa bearing BALB/c nude mice, dynamical MR imaging is carried out using a 3.0T imaging system. The Signal intensity(SI) of tumor regions is analyzed to evaluate its targeting ability in vivo. Meanwhile, the tumors of mices were irradiated by the 808 nm NIR laser and the changes of tumors volume were measured in order to study the photothermal efficiency.Result:(1) TEM reveals the prepared USPION has an average size of 6 nm with a spherical shape and good monodispersity. XRD confirms that USPION consists of Fe3O4 nanoparticles. USPION has high relaxations, with The T2 relaxivity value of 85.3 m M-1S-1, indicating USPION could be used as a promising negative MR imaging contrast agent. FTIR spectra demonstrate the successful conjugation of USPION and Bn in the prepared USPION@Bn. Absorbance spectra determined by a UV-Vis-NIR spectrophotometer shows high absorbance values in the NIR region. after irradiation of the NIR 808 nm laser at the power density of 3.0 W/cm2 for 10 min, the temperature of the USPION@Bn solution at the concentration of 1 mg/m L could increase by 19.9?.(2) The outcome of MTT assays suggest that USPION@Bn nanoparticles produce no obvious inhibition of cells growth when their concentrations are below 200 ?g/m L. In vitro relaxivity characterizations of USPION@Bn and USPION were compared. Cells treated with USPION@Bn nanoprobes exhibited much lower MR signals than the treatment of USPION accounting for the active targeted ability of USPION@Bn towards prostate cancer. Calcein-AM/PI staining reveals USPION@Bn nanoparticles can efficiently induce the death of tumor cells.(3) Tumor xenograft model was successfully established using subcutaneous implantation method. The hypotensive T2 signal could be observed in tumor region after the injection of USPION@Bn, which shows significant difference from that of the pre-injection MR imaging. Furthermore, in vitro photothermal treatment tests demonstrate that the tumor growth can be efficiently inhibited by the photothermal effects of the Au/PPY@Fe3O4 nanocomposites irradiated by NIR, indicating that USPION@Bn is a good photothermal therapy agent.Conclusion: The magnetic molecular probes USPION@Bn are successfully fabricated. The prepared nanoprobes own the merits of good biocompatibility, receptor specific cancer targeting ability, excellent magnetic properties in the MR imaging and high efficiency in photothermal conversion, suggesting that they have great potential in simultaneous MR imaging-guided cancer theranostic applications.