锰掺杂低聚水飞蓟超分子网络诊疗一体平台的开发与性能分析  

Development of Manganese Doped Oligomeric Silymarin Supramolecular Network Diagnosis and Treatment Nanoplatform

作　　者：柯月 马志方[1] 石强[1,2] KE Yue;MA Zhi-Fang;SHI Qiang(State Key Laboratory of Polymer Physics and Chemistry,Changchun Institute of Applied Chemistry,Chinese Academy of Sciences,Changchun 130022,China;School of Applied Chemistry and Engineering,University of Science and Technology of China,Hefei 230026,China)

机构地区：[1]中国科学院长春应用化学研究所,高分子物理与化学国家重点实验室,长春130022 [2]中国科学技术大学应用化学与工程学院,合肥230026

出　　处：《分析化学》2023年第11期1783-1792,共10页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金项目(Nos.51573186,52061135202)资助

摘　　要：利用一锅法将甲醛缩合的多酚类抗肿瘤活性药物水飞蓟低聚物与锰配位,制备出具有酸响应降解特性的聚乙烯吡咯烷酮-低聚水飞蓟-锰三组分组装的金属-酚醛超分子网络纳米结构(PSM)。对PSM的粒径分布与形貌进行了表征,筛选出最佳的水飞蓟-氯化锰投料质量比(2∶1)。通过高分辨透射电子显微镜(HRTEM)、傅里叶变换红外光谱(FTIR)、X射线光电子能谱(XPS)、粉末X射线衍射(XRD)和热重分析(TGA)对制备的样品进行形貌结构表征及元素分布分析,采用紫外-可见(UV-Vis)吸收光谱评估了PSM纳米结构作为药物载体负载模型药物罗丹明B(RB)的潜能。药物释放曲线和体外降解实验证实PSM纳米结构具有酸性响应降解释放RB的性质。采用不同浓度梯度PSM纳米结构分散液进行体外磁共振成像(MRI),探究了PSM纳米结构在不同缓冲体系中的MRI成像能力,并通过体内荷瘤小鼠MRI实验评估了其体内成像性能。结果表明,PSM纳米结构的MRI性能具有浓度梯度依赖性,并且在酸性环境中成像能力增强,pH=6.5时弛豫率r_(1)由8.8 L/(mmol·S)增至10.1 L/(mmol·S);并且在体内具有更长的循环时间,在体内留存至少24 h,而离子溶液在6 h内便被快速清除。体外抗肿瘤细胞活性实验结果表明,浓度低于100μg/mL的PSM纳米结构具有较好的癌细胞杀伤能力。The polyvinylpyrrolidone(PVP)-oligomeric silymarin-manganese three-component-assembled metalphenolic supramolecular network nanostructured microspheres(PSM)with acid-responsive degradation characteristics were prepared by coordinating formaldehyde condensed oligomers of the polyphenolic antitumoractive drug silymarin with manganese chloride using a one-pot method.The optimal mass feed ratio of silymarin to manganese chloride(2:1)was selected from the perspectives of particle size and morphology distribution through a nanoparticle size analyzer and transmission electron microscopy(TEM).The morphology,structure and elemental distribution of the prepared samples were characterized by high-resolution transmission electron microscopy(TEM),Fourier transform infrared spectroscopy(FTIR),X-ray photoelectron spectroscopy(XPS),powder X-ray diffraction(XRD),and thermogravimetric analysis(TGA).Subsequently,the potential ofPSM nanoparticles as drug carriers for loading model drug Rhodamine B(RB)was evaluated through UV-vis absorption spectroscopy.The drug release curve and in vitro degradation experiments jointly confirmed that PSM couold respond to acid change.To investigate the magnetic resonance imaging(MRI)ability of PSM in different buffer systems,in vitro and in vivo imaging were performed on PSM dispersions with different concentration gradients.The results indicated that PSM had concentration gradient-dependent magnetic resonance imaging performance and enhanced imaging ability in acidic environments.At pH 6.5,the relaxation rate r_(1)increased from 8.8 to 10.1 L/(mmol·S).Furthermore,it had a longer circulation time in vivo,which remained for at least 24 h compared to MnCl_(2)within 6 h.In addition,4T1 mice breast tumor cell viability experiments in vitro showed that PSM had anti-tumor capability below the concentration of 100μg/mL.

关 键 词：超分子网络 磁共振成像 抗癌 诊疗一体化 

分 类 号：R96[医药卫生—药理学] O641.3[医药卫生—药学]