Sdudy On The Preparation Of Multifunctional Contrast Agents And Their Application In Theranostics

Molecular imaging is of significant importance for early detection and diagnosis of cancer.Multifunctional imaging techniques can yield complementary diagnostic information and offer synergistic advantages over the single modality.The incorporation of magnetic resonance imaging?MRI?and optical imaging technology can ultimately to achieve functional imaging and structure imaging,providing high resolution rate of histologic structure information and realizing high sensitive detection at the same time.Furthermore,the image quality can also be improved,leading to a more accurate diagnosis.Therefore,the strategy of combining MRI contrast agents and optical components into a single particle has brought about high speed development and widespread applications.On the other hand,the design and construction of a proper theranostic platform with diagnostic capabilities and simultaneously release drugs attracted considerable research interest.Imaging guidance could be utilized to identify the tumor sites before treatment or visualize the procedure during treatment in real time,providing valuable information to enhance anti-cancer efficacy and optimize therapy with greater safety,accuracy and sensitivity.Herein,a novel core-shell magnetic microsphere for dual modal MR and optical imaging was produced by one-pot emulsifier-free emulsion polymerization,which could provide high resolution rate of histologic structure information and realize high sensitive detection at the same time.The synthesized magnetic microspheres composed of cores containing oleic acid?OA?and sodium undecylenate?NaUA?modified Fe₃O₄ nanoparticles and styrene?St?,Glycidyl methacrylate?GMA?,and polymerizable lanthanide complexes?Gd?AA?₃Phen and Eu?AA?₃Phen?polymerized on the surface for outer shells.Fluorescence spectra show characteristic emission peaks from Eu³⁺at 590 nm and 615 nm and vivid red luminescence can be observed by 2-photon confocal scanning laser microscopy?CLSM?.In vitro cytotoxicity tests based on the MTT assay demonstrate good cytocompatibility,the composites have longitudinal relaxivity value r₁=8.39 mM^-1s^-1and also have transverse relaxivity value r₂=71.18 m M^-1s^-1at clinical 3.0 T magnetic resonance scanner.In vitro and in vivo MRI studies exhibit high signal enhancement on both T₁-and T₂-weighted MR images.These fascinating multifunctional properties suggest that the polymer microspheres have large clinical potential as multi-modal MRI/optical probes.Similarly,a kind of organic/inorganic hybrid polymer microspheres?CuS@copolymer?encapsuted CuS NPs for MRI-guided chemo-photothermal therapy was simply prepared via emulsifier-free emulsion polymerization with the full participation of hydrophilic CuS NPs,St,N-isopropylacrylamide?NIPAm?,methacrylic acid?MAA?,and polymerizable complex Gd?AA?₃Phen.The synthesized multifunctional microspheres with excellent biocompatibility exhibited high drug loading?15.3 wt%for doxorubicin hydrochloride?DOX·HCl??and excellent drug release under low pH and high temperature.The photosensitive CuS cores which can simultaneously efficiently absorb near infrared?NIR?light and convert NIR light to fatal heat,leading to synergistic effects integrated photothermal therapy?PTT?with chemo-therapy.Moreover,the temperature sensitive copolymer attached onto the CuS NPs was able to be productively infected by the thermal effect and gave rise to a highly controllable DOX release.Furthermore,the CuS@copolymer/DOX showed an enhanced therapeutic efficacy against 4T1 cells than separate photothermal therapy or chemotherapy.Additionally,the drug delivery procedure could be visualized by in vivo MR images and the longitudinal relaxivity?r₁?was computed to be 10.72 mM^-1s^-1.These results suggest CuS@copolymer microspheres highly attractive candidates for biomedical applications.