Sun Wenjie, Dong Xiaojuan, Huang Pingping, Shan Jia, Qi Lei, Zhou Jun
State Key Laboratory of Ophthalmology, Optometry and Visual Science, Institute of Advanced Materials for Nano-Bio Applications, School of Ophthalmology and Optometry, School of Biomedical Engineering, Wenzhou Medical University Wenzhou 325035 China
Center for Reproductive Medicine, Naval Medical Center of PLA, Second Military Medical University Shanghai 200052 China.
RSC Adv. 2021 Nov 17;11(58):36920-36927. doi: 10.1039/d1ra06548c. eCollection 2021 Nov 10.
Titania (TiO) nanomaterials have been proved to be biocompatible sonosensitizers for sonodynamic therapy (SDT) of various cancer cells, while they suffer from weak sonodynamic effects due to fast combination of excited carriers. In this work, to improve the therapeutic efficiency, we prepared PEGylated Nb-doped TiO (TiO :Nb) nanoparticles by a simple solvothermal method and a subsequent surface modification process. The TiO :Nb nanoparticles exhibited an average size of 11 nm and a polydisperse index of 0.12. The Nb doping had no obvious effect on the phase of TiO matrixes but released electrons to the conduction band of TiO, resulting in high concentrations of deficiencies. As a result, the TiO :Nb nanoparticles exhibited a higher efficiency of singlet oxygen (O) generation than that of pure TiO nanoparticles upon ultrasound irradiation. Importantly, the TiO :Nb nanoparticles had high biocompatibility similar to pure TiO nanoparticles, while they could efficiently produce cytotoxic O to destroy cancer cells in comparison to the partially destroyed cancer cells by pure TiO nanoparticles upon ultrasound irradiation. More importantly, the TiO :Nb nanoparticles displayed obvious tumor cellular injury in tumor-bearing mice through high SDT effects. Therefore, the synthesized PEGylated TiO :Nb nanoparticles in this study exhibited higher therapeutic effects of SDT than that of the pure TiO nanoparticles, and the doping strategy would provide some insights for tuning traditional weak sonosensitizers into efficient ones.
二氧化钛（TiO）纳米材料已被证明是用于多种癌细胞声动力疗法（SDT）的生物相容性声敏剂，然而由于激发载流子的快速复合，它们的声动力效应较弱。在这项工作中，为了提高治疗效率，我们通过简单的溶剂热法和后续的表面改性工艺制备了聚乙二醇化的铌掺杂TiO（TiO:Nb）纳米颗粒。TiO:Nb纳米颗粒的平均尺寸为11 nm，多分散指数为0.12。铌掺杂对TiO基体的相没有明显影响，但向TiO的导带释放电子，导致高浓度的缺陷。结果，在超声照射下，TiO:Nb纳米颗粒产生单线态氧（O）的效率高于纯TiO纳米颗粒。重要的是，TiO:Nb纳米颗粒具有与纯TiO纳米颗粒相似的高生物相容性，而与超声照射下被纯TiO纳米颗粒部分破坏的癌细胞相比，它们能有效地产生细胞毒性O来破坏癌细胞。更重要的是，TiO:Nb纳米颗粒通过高SDT效应在荷瘤小鼠中显示出明显的肿瘤细胞损伤。因此，本研究中合成的聚乙二醇化TiO:Nb纳米颗粒表现出比纯TiO纳米颗粒更高的SDT治疗效果，并且这种掺杂策略将为将传统的弱声敏剂调制成高效声敏剂提供一些见解。
