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磁性纳米颗粒产生的活性氧用于抗菌及体内肿瘤治疗

Anti-bacterial and in vivo tumor treatment by reactive oxygen species generated by magnetic nanoparticles.

作者信息

Zhang Di, Zhao Ying-Xi, Gao Yu-Juan, Gao Fu-Ping, Fan Yun-Shan, Li Xiao-Jun, Duan Zhong-Yu, Wang Hao

机构信息

CAS Key Laboratory for Biological Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology (NCNST), No. 11 Beiyitiao Zhongguancun Haidian District, Beijing, 100190, China.

出版信息

J Mater Chem B. 2013 Oct 14;1(38):5100-5107. doi: 10.1039/c3tb20907e. Epub 2013 Aug 23.

Abstract

Photodynamic therapy is widely used in clinics and for anti-bacterial applications. The major challenge is the limited depth of tissue penetration of light and poor targetability. In this study, magnetite nanoparticles were used as a highly sensitive T-weighted MR imaging contrast agents to target the tumor and mimic horseradish peroxidase (HRP), which could catalyze the decomposition of hydrogen peroxide to generate reactive oxygen species (ROS) to inhibit the tumor in vivo. In these experiments, MNPs were demonstrated to possess the enzyme-mimicking activity in different pH values, and the activity was dependent on the size of the MNPs: the smaller the size, the higher the activity. We demonstrated that MNPs showed highly efficient anti-bacterial (E. coli) activity in presence of HO. The E. coli inhibition ratio reached nearly 100% at optimal concentration. The anti-tumor activity was evaluated through HeLa cell viability under treatment with MNPs and HO. Consequently, the cell viability was significantly decreased and more than 80% of HeLa cells were dead after treatment with MNPs and HO under different pH values. MR imaging was used to demonstrate the tumor targetability of 13 nm MNPs in vitro and in vivo. Consequently, the relaxivity of the 13 nm MNPs was determined to be r = 104 s mM. The MR signal was much more negative and the intensity was significantly diminished with the increase of the concentration of 13 nm MNPs in vitro. The tumor signal was clearly visualized and a 3-fold decrease of the MR signal intensity of the tumor site of the mice was observed after 24 h-post treatment with the 13 nm MNPs. Finally, the tumor inhibition in vivo was investigated using 6 nm MNPs in BALB/c nude female mice bearing subcutaneously implanted HeLa cells on the right flank. The results show statistically significant efficacy in delaying tumor growth from day 6, and an approximately 99% tumor inhibition ratio was shown by the combination of MNPs and HO after treatment for 17 days. By leveraging the passive targeting and MR imaging properties, we expect that the enzyme-mimicking MNPs could be used for cancer theranostics and may open up a new avenue for the treatment of epidermal infections.

摘要

光动力疗法在临床上和抗菌应用中被广泛使用。主要挑战在于光的组织穿透深度有限以及靶向性差。在本研究中,磁铁矿纳米颗粒被用作高灵敏度的T加权磁共振成像造影剂来靶向肿瘤,并模拟辣根过氧化物酶(HRP),其可催化过氧化氢分解产生活性氧(ROS)以在体内抑制肿瘤。在这些实验中,证明了磁性纳米颗粒在不同pH值下具有模拟酶的活性,且该活性取决于磁性纳米颗粒的尺寸:尺寸越小,活性越高。我们证明了磁性纳米颗粒在过氧化氢存在下表现出高效的抗菌(大肠杆菌)活性。在最佳浓度下,大肠杆菌抑制率接近100%。通过在磁性纳米颗粒和过氧化氢处理下HeLa细胞的活力来评估抗肿瘤活性。因此,在不同pH值下用磁性纳米颗粒和过氧化氢处理后,细胞活力显著降低,超过80%的HeLa细胞死亡。磁共振成像用于证明13纳米磁性纳米颗粒在体外和体内的肿瘤靶向性。因此,确定13纳米磁性纳米颗粒的弛豫率为r = 104 s mM。在体外,随着13纳米磁性纳米颗粒浓度的增加,磁共振信号变得更负且强度显著降低。在用13纳米磁性纳米颗粒处理24小时后,肿瘤信号清晰可见,并且观察到小鼠肿瘤部位的磁共振信号强度降低了3倍。最后,在右侧腹皮下植入HeLa细胞的BALB/c裸鼠雌性小鼠中使用6纳米磁性纳米颗粒研究体内肿瘤抑制情况。结果显示从第6天起在延迟肿瘤生长方面具有统计学显著疗效,并且在处理17天后,磁性纳米颗粒和过氧化氢的组合显示出约99%的肿瘤抑制率。通过利用被动靶向和磁共振成像特性,我们期望模拟酶的磁性纳米颗粒可用于癌症诊疗,并可能为表皮感染的治疗开辟一条新途径。

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