Li Meifang, Zhao Qi, Yi Xuan, Zhong Xiaoyan, Song Guosheng, Chai Zhifang, Liu Zhuang, Yang Kai
School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Medical College of Soochow University , Suzhou, Jiangsu 215123, China.
Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Institute of Functional Nano & Soft Materials Laboratory (FUNSOM), Soochow University , Suzhou, Jiangsu 215123, China.
ACS Appl Mater Interfaces. 2016 Apr 20;8(15):9557-64. doi: 10.1021/acsami.5b11588. Epub 2016 Apr 7.
Although conventional radiotherapy (RT) has been widely used in the clinic to treat cancer, it often has limited therapeutic outcomes and severe toxic effects. There is still a need to develop theranostic agents with both imaging and RT-enhancing functions to improve the accuracy and efficiency of RT. Herein we synthesize Au@MnS@ZnS core/shell/shell nanoparticles with polyethylene glycol (PEG) functionalization, yielding Au@MnS@ZnS-PEG nanoparticles with great stability in different physiological solutions and no significant cytotoxicity. It is found that Au@MnS@ZnS-PEG nanoparticles can enhance the cancer cell killing efficiency induced by RT, as evidenced by multiple in vitro assays. Owing to the existence of paramagnetic Mn(2+) in the nanoparticle shell, our Au@MnS@ZnS-PEG can be used as a contrast agent for T1-weighted magnetic resonance (MR) imaging, which reveals the efficient accumulation and retention of nanoparticles in the tumors of mice after intravenous injection. Importantly, by exposing tumor-bearing mice that were injected with Au@MnS@ZnS-PEG to X-ray irradiation, the tumor growth can be significantly inhibited. This result shows clearly improved therapeutic efficacy compared to RT alone. Furthermore, no obvious side effect of Au@MnS@ZnS-PEG is observed in the injected mice. Therefore, our work presents a new type of radiosensitizing agent, which is promising for the imaging-guided enhanced RT treatment of cancer.
尽管传统放疗(RT)已在临床上广泛用于治疗癌症,但它的治疗效果往往有限且毒副作用严重。仍然需要开发具有成像和放疗增强功能的诊疗剂,以提高放疗的准确性和效率。在此,我们合成了具有聚乙二醇(PEG)功能化的Au@MnS@ZnS核/壳/壳纳米颗粒,得到了在不同生理溶液中具有高稳定性且无明显细胞毒性的Au@MnS@ZnS-PEG纳米颗粒。多项体外实验证明,Au@MnS@ZnS-PEG纳米颗粒能够提高放疗诱导的癌细胞杀伤效率。由于纳米颗粒壳层中存在顺磁性的Mn(2+),我们的Au@MnS@ZnS-PEG可作为T1加权磁共振(MR)成像的造影剂,它显示了纳米颗粒在静脉注射后在小鼠肿瘤中的有效积累和滞留。重要的是,通过对注射了Au@MnS@ZnS-PEG的荷瘤小鼠进行X射线照射,肿瘤生长可得到显著抑制。与单独放疗相比,这一结果显示出明显提高的治疗效果。此外,在注射的小鼠中未观察到Au@MnS@ZnS-PEG有明显的副作用。因此,我们的工作提出了一种新型的放射增敏剂,有望用于癌症的成像引导增强放疗治疗。