Preparation Of Multifunctional Nanomaterials And Application In Magnetic Resonance Imaging

Early sensitive diagnosis and precision treatment of cancer are hotspots and difficulties in the relevant research fields.Magnetic resonance imaging（MRI）technology stands out among various clinical biomedical imaging technologies due to its advantages in terms of non-invasive,deep penetration,and non-ionizing radiation detection.Conventional MRI is based on the differences in hydrogen atom content and relaxation time to from imaging.However,due to the minor differences in hydrogen proton relaxation rates between pathological tissue in the early stages of tumors and normal tissue,imaging contrast is insufficient,resulting in inaccurate actual diagnosis.In this regard,gadolinium-based contrast agents（Gd CAs）,such as Gd-DTPA and Gd-DOTA,are widely applied to enhance the T₁ relaxivity and improve the accuracy of clinical diagnosis.Nevertheless,commercial Gd CAs were restricted to rapid renal clearance and low relaxivity.Furthermore,the leakage of toxic Gd ion in Gd CAs due to inadequate chelates stability,could exacerbate nephrogenic systemic fibrosis or deposit in the heart,kidney,skin,and even in the brain,threatening the patient’s health.To address these issues,a series of nanoprobes were specifically designed and prepared as MRI contrast agents.The main research contents are as follows:1.Single-atom Gd nano-contrast agent with robust stability and good tumor targeting ability were designed to mimic the Gd complex.Specifically,single-atom Gd was anchored on nitrogen-doped carbon matrix（Gd-N_xC）through the spatial-confinement method,which was further subjected to controllable chemical etching to afford fully etched bowl-shape Gd-N_xC（fe Gd-N_xC）with hydrophilic properties and defined Gd coordination structure,similar to commercial Gd complex.Such nanostructures maximized Gd sites exposure for highly sensitive MRI.Longitudinal（r₁）and transverse relaxivity（r₂）of fe Gd-N_xC at 3 T were 34.2 and 80.1 m M^-1 s^-1（far higher than that of commercial Gd-DTPA）,respectively.Moreover,the strong electron localization and interaction between Gd and N atoms afforded excellent kinetic inertness and thermal stability for fe Gd-N_xC.No significant Gd³⁺leaching was observed even incubated with 5 equiv.Cu²⁺.These fe Gd-N_xC nanoprobes allowed for passitive targeting toward tumor site due to their favorable size and excellent stability,which is conducive to targeted tumor specific imaging.Imaging studies in vivo demonstrated that fe Gd-N_xC displays T₁/T₂ dual-mode MRI ability in mice subcutaneous tumor models.This work provides a creative design protocol for high-performance single-atom MRI contrast agents.2.An intrinsic hydrophilic iron single-atom bowl-shaped nanoprobe（Fe-SANB）was developed for magnetic resonance imaging（MRI）-guided tumor microenvironment-triggered cancer therapy.Benefiting from the sufficient exposure of Fe single-atom and excellent hydrophilicity of bowl-shape structure,the Fe-SANBs exhibited a superior performance for T₁-weighted MRI with a r₁value of 11.48 m M^-1 s^-1,which is three-fold higher than that of the commercial Gd-DTPA(r₁=3.72 m M^-1 s^-1).In tumor microenvironment（TME）,the Fe-SANBs with Fe-N₄ structure can trigger p H-induced Fenton-like activity to generate highly toxic hydroxyl radicals for high-efficiency chemodynamic therapy（CDT）.The Fe（II）/Fe（III）ratio in Fe-SANBs was tailored by adjusting the calcination temperature,and the samples obtained the optimal combination efficiency of MRI and CDT at 700℃.Furthermore,the generation of·OH at the tumor site was accelerated via the photothermal effect of the Fe-SANBs,thus promoting CDT efficacy.Both in vitro and in vivo results confirmed that our nanoplatform exhibited high T₁-weighted MRI contrast,robust biocompatibility,and satisfactory tumor treatment,providing a potential multifunctional nanoplatform for MRI-guided TME-triggered precise cancer therapy.3.A Mn-based nanoprobe（Mn-TiO₂）with strong T₁ relaxivity was constructed for highly sensitive MRI in tumor diagnosis.First,the ultra-thin fluorinated nanosheets were synthesized by hydrothermal method.Then Na OH etching was used to remove unstable fluoride ions on the surface of the nanosheets,to improve its hydrophilicity and surface negative charge.Subsequently,Mn²⁺was added to in situ synthesize manganese hydroxide on the nanosheet surface,imparting MRI functionality to the nanosheets.Finally,polyethylene glycol was coated on the surface of nanosheets to increase its water solubility and biocompatibility further.The nanosheets possess a large specific surface area,providing abundant attachment sites for magnetic metal ions(Mn²⁺).Additionally,the poor crystallinity of loaded manganese hydroxide enhances the interaction between Mn²⁺and water molecules,resulting in high utilization efficiency of Mn atoms and favorable properties of MRI(r₁ value of42.5 m M^-1 s^-1 at clinical field strength).Compared to commercial Gd-DTPA probes,the Mn-TiO₂ probe exhibited significantly enhanced T₁-weighted MRI contrast in subcutaneous tumor models in mice.In an orthotopic liver cancer model,the Mn-TiO₂ probe demonstrated efficient T₁-weighted MRI performance for localized tumors while effectively distinguishing tumor lesions from normal liver tissue.This work provides an efficient new MRI probe for precise tumor localization.