pH响应性掺锰非晶态碳酸钙纳米颗粒的制备及其在小鼠乳腺癌磁共振成像中的研究OA
Preparation of pH-responsive manganese-doped amorphous calcium carbonate nanoparticles and their application in magnetic resonance imaging of mouse breast cancer
目的 制备一种pH响应性锰掺杂的非晶态碳酸钙纳米颗粒Mn@ACC/PAA,验证其作为MRI对比剂体外弛豫能力、体内肿瘤靶向成像效果,同时全面考察细胞毒性、血液相容性等生物安全性指标.方法 本研究通过透射电子显微镜表征纳米材料形貌,采用动态光散射仪测定水合动力学直径,并联合多种光谱技术解析材料性质:紫外-可见吸收光谱分析光吸收特性,X射线衍射仪鉴定晶体结构,傅里叶变换红外光谱仪检测表面官能团,X射线光电子能谱揭示元素组成与化学状态.进一步使用1.0 T小动物核磁共振成像系统评估Mn@ACC/PAA的MRI成像性能,同时通过CCK-8细胞毒性实验及溶血实验综合评价其生物安全性.结果 成功制备粒径约16.29 nm的近球形Mn@ACC/PAA纳米颗粒,溶液分散性与单分散性良好.该Mn掺杂非晶碳酸钙材料在酸性条件下(pH=5.5)能有效释放锰离子,其纵向弛豫率(r1)达18.07mM-1·s-1,表现出优异的T1磁共振造影性能,可增强病灶对比度.同时,该材料对小鼠胚胎成纤维细胞系细胞(NHI/3T3)毒性低,且对小鼠乳腺肿瘤细胞系(4T1)具有浓度依赖性杀伤作用.溶血性低,生物相容性良好.结论 研究发现,通过Mn掺杂制备的pH响应性非晶态碳酸钙纳米颗粒不仅能够实现高效的T1加权磁共振成像,还表现出优异的生物相容性,这为其在肿瘤诊断等临床领域的应用开辟了新途径.
Objective To prepare a pH-responsive Mn-doped amorphous calcium carbonate nanoparticle(Mn@ACC/PAA),and to assess its efficacy as MRI contrast agents through in vitro relaxivity and in vivo tumor-targeted imaging,along with comprehensive biosafety evaluation including cytotoxicity and blood compatibility.Methods The morphology of the nanomaterials was characterized using transmission electron microscopy.The hydrodynamic diameter was measured by dynamic light scattering.Additionally,the material properties were analyzed through a combination of spectroscopic techniques:ultraviolet-visible absorption spectroscopy was employed to examine light absorption characteristics,X-ray diffraction to identify crystal structures,Fourier-transform infrared spectroscopy to detect surface functional groups,and X-ray photoelectron spectroscopy to reveal elemental composition and chemical states.The MRI performance of the Mn@ACC/PAA was evaluated with 1.0T small animal MRI system;and its biosafety was assessed via Cell Counting Kit-8(CCK-8)assays and hemolysis tests.Results Spherical Mn@ACC/PAA nanoparticles(with a diameter of 16.29 nm)were prepared successfully,they exhibited good solution dispersibility and monodispersity.The particles released Mn2+under acidic conditions(pH 5.5),achieving high r1(18.07 mM-1·s-1)for enhanced T1-weighted contrast.The material showed low toxicity to mouse embryonic fibroblast cell line NHI/3T3 but concentration-dependent cytotoxicity to mouse mammary tumor cell line 4T1,with minimal hemolysis and good biocompatibility.Conclusion The pH-responsive amorphous calcium carbonate nanoparticles prepared via manganese doping not only enable efficient T1-weighted magnetic resonance imaging but also demonstrate excellent biocompatibility,which opens new avenues for their application in clinical fields such as tumor diagnosis.
薛小格;刘顶华;邱裕友
安徽理工大学第一附属医院,安徽淮南 232007上海纳米催化医学前沿科学中心,同济大学医学院生物医学工程与纳米科学研究所,上海 200065同济大学附属第十人民医院放射科,上海 200072
医药卫生
pH响应T1磁共振成像对比剂肿瘤诊断显像
pH-responsiveT1 magnetic resonance imaging contrast agenttumordiagnostic imaging
《同济大学学报(医学版)》 2026 (2)
194-203,10
国家自然科学基金(12471357)上海市卫生健康委员会智慧医疗专项项目(2025ZHYL020)上海市科学技术委员会基础研究计划"探索者计划"(25TS1406100)
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