量子ドットによる新規セラノスティックナノ粒子の開発

我们开发了新的治疗诊断纳米颗粒，基于量子点（QD），与多自旋氮氧化物-环糊精（QD@CD-TEMPO和QD@CD-TEMPOH）和三苯基膦（TPP）共轭。这两种传感器都适用于活细胞和组织的氧化应激和氧化还原状态的定量成像分析。这些纳米颗粒联合收割机结合了几个特点：（i）三种成像模式（MRI，EPR，光学）;（ii）由于TPP，细胞内递送和定位主要进入线粒体;（iii）由于TPP，可以感知和可视化活细胞和组织中的氧化应激和氧化还原状态区域–。基于氧化剂和还原剂之间的平衡，它们的对比特性的动力学;（iv）氧化还原调节活性和诱导癌细胞凋亡的可能性，由于氮氧化物残基的SOD模拟特征，对正常细胞的活力没有显著影响。体外诱导线粒体功能障碍培养细胞中氧化应激和总还原能力的EPR/光学成像。还分析了对正常细胞和癌细胞的细胞毒性和凋亡诱导（MTS测定，Annexin-V测试）。氧化应激诱导的肾功能不全动物的MR成像。

We developed new theranostic nanoparticles, based on quantum dots (QDs), conjugated with multispin nitroxide-cyclodextrins (QD@CD-TEMPO and QD@CD-TEMPOH) and triphenylphosphonium (TPP). Both sensors are applicable for quantitative imaging assays of oxidative stress and redox-status of living cells and tissues.These nanoparticles combine several features: (i) three imaging modalities (MRI, EPR, optical); (ii) intracellular delivery and localization mainly into the mitochondria due to TPP; (iii) possibility to sense and visualize the areas of oxidative stress and redox-status in living cells and tissues – due to dynamics of their contrast properties, based on the balance between oxidizers and reducers; (iv) redox-modulating activity and possibility to induce apoptosis in cancer cells, without significant effect on viability of normal cells due to SOD-mimetic feature of nitroxide residues.The analytical tests using both sensors were validated by conventional redox analyses (mitoSOX, DHE, DCF, TAC).Both sensors were applied for:1. EPR/optical imaging of oxidative stress and total reducing capacity in cultured cells with exogenously induced mitochondrial dysfunction. Cytotoxicity and induction of apoptosis on normal and cancer cells were also analysed (MTS assay, Annexin-V test).2. MR imaging in animals with kidney dysfunction, induced by oxidative stress.