Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors
Ball-in-ball ZrO2 nanostructure for simultaneous CT imaging and highly efficient synergic microwave ablation and tri-stimuli-responsive chemotherapy of tumors
复制标题
球中球ZrO2纳米结构用于同步CT成像以及肿瘤的高效协同微波消融和三刺激化疗
DOI：
10.1039/c7nr02511d
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发表时间：
2017-07-07
期刊：
影响因子：
6.7
通讯作者：
Meng, Xianwei
中科院分区：
文献类型：
--
作者：
Long, Dan;Niu, Meng;Meng, Xianwei
与单独热疗和化疗相比，热化疗联合治疗显示出突出的协同治疗效果。在此，我们开发了一种基于新型球中球结构ZrO2纳米颗粒（BB-ZrO2 NPs）的智能三刺激反应药物递送系统，该系统涉及X@BB-ZrO2 NPs （X代表负载IL， DOX，角蛋白和十四醇）。由于特殊的两层中空纳米结构的自反射和空间约束效应的共同作用，BB-ZrO2 NPs的微波能量转换效率比传统单层NPs高41.2%。三刺激响应控释策略表明，基于角蛋白和十四醇的单一NPs中整合pH、氧化还原和微波可以有效提高DOX的特异性控释。在pH = 7.2, GSH = 20 μ m的PBS中，DOX的释放量仅为8.1%，而在pH = 5.5, GSH = 13 mM的肿瘤部位，微波消融下DOX的释放量可达50%左右。制备的X@BB-ZrO2 NPs对皮下肿瘤（H22荷瘤小鼠）和深部肿瘤（肝移植VX2荷瘤兔模型）均表现出良好的化疗和微波消融协同治疗作用。X@ BB-ZrO2 + MW组在皮下肿瘤治疗42(d)天内无复发和死亡。术后6 d，对照组、MW组和X@ BB-ZrO2 + MW组深部肿瘤的生长速率分别为290.1%、14.1%和-42%。采用双源CT监测自制BB-ZrO2 NPs的代谢行为，采用传统CT监测兔肿瘤生长情况。冷冻切片检查和ICP结果表明，三刺激响应的控释策略精确控制了药物的传递和增强了细胞毒性。具有高微波能量转换效率的球中ZrO2 NPs首次被开发用于协同微波消融和三刺激反应化疗，具有潜在的应用前景
Combined thermo-chemotherapy displays outstanding synergically therapeutic efficiency when compared with standalone thermotherapy and chemotherapy. Herein, we developed a smart tri-stimuliresponsive drug delivery system involving X@BB-ZrO2 NPs (X represents loaded IL, DOX, keratin and tetradecanol) based on novel ball-in-ball-structured ZrO2 nanoparticles (BB-ZrO2 NPs). The microwave energy conversion efficiency of BB-ZrO2 NPs was 41.2% higher than that of traditional single-layer NPs due to the cooperative action of self-reflection and spatial confinement effect of the special two-layer hollow nanostructure. The tri-stimuli-responsive controlled release strategy indicate that integrated pH, redox and microwaves in single NPs based on keratin and tetradecanol could effectively enhance the specific controlled release of DOX. The release of DOX was only 8.1% in PBS with pH = 7.2 and GSH = 20 mu M. However, the release could reach about 50% at the tumor site (pH = 5.5, GSH = 13 mM) under microwave ablation. The as-made X@BB-ZrO2 NPs exhibited perfect synergic therapy effect of chemotherapy and microwave ablation both in subcutaneous tumors (H22 tumor-bearing mice) and deep tumors (liver transplantation VX2 tumor-bearing rabbit model). There was no recurrence and death in the X@ BB-ZrO2 + MW group during the therapy of subcutaneous tumors even on the 42(nd) day. The growth rates in the deep tumor of the control, MW and X@ BB-ZrO2 + MW groups were 290.1%, 14.1% and -42% 6 days after ablation, respectively. Dual-source CT was used to monitor the metabolism behavior of the as-made BB-ZrO2 NPs and traditional CT was utilized to monitor the tumor growth in rabbits. Frozen section examination and ICP results indicated the precise control of drug delivery and enhanced cytotoxicity by the tri-stimuli-responsive controlled release strategy. The ball-in-ball ZrO2 NPs with high microwave energy conversion efficiency were first developed for synergic microwave ablation and tristimuli- responsive chemotherapy, which may have potential applications