MnO2-DNAzyme-photosensitizer nanocomposite with AIE characteristic for cell imaging and photodynamic-gene therapy
MnO2-DNAzyme-photosensitizer nanocomposite with AIE characteristic for cell imaging and photodynamic-gene therapy
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DOI：
10.1016/j.talanta.2019.05.003
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发表时间：
2019-09-01
期刊：
影响因子：
6.1
通讯作者：
Xia, Fan
中科院分区：
文献类型：
--
作者：
Wang, Xudong;Dai, Jun;Xia, Fan
光动力疗法（PDT）被认为是一种有效的治疗方法。而光动力疗法由于照射强度随深度的增加而降低以及肿瘤组织缺氧，不足以达到有效治疗。基因治疗和光动力学治疗相结合已成为提高治疗效果的有效策略。在本研究中，GSH响应MnO 2被用于递送TB和DNAzyme用于癌症成像和PDT-基因组合治疗。TB是一种具有聚集诱导发射特性的光敏剂，用于光动力治疗，而DNAzyme作为EGR-1 mRNA降解的催化剂，用于基因沉默。所有体外肿瘤治疗的结果表明，MnO 2-DNAzyme-TB纳米复合物（MDT）可以内化到细胞中。随后，MDT可通过基因沉默降低EGR-1的表达，从而抑制细胞生长。此外，由聚集的TB产生的单线态氧能够进一步抑制细胞生长。光动力疗法与基因疗法的联合应用大大提高了抗肿瘤的效率。此外，体内肿瘤治疗实验表明，光照下的MDT可以通过光动力和基因沉默联合治疗有效抑制MCF-7荷瘤小鼠的肿瘤生长。
Photodynamic therapy (PDT) was considered as an effective treatment. Whereas only PDT is not enough to achieve effective therapy on account of irradiation intensity decreases as depth increases as well as tumor hypoxia. Combination with gene therapy and photodynamic therapy have emerged as an effective strategy to improve therapeutic effectiveness. In the present study, a GSH responsive MnO2 was employed to delivery TB and DNAzyme for cancer imaging and PDT-gene combination treatment. TB, a photosensiters with aggregation-induced emission characteristic, was employed for photodynamic therapy, while DNAzyme, acting as catalysts for the degradation of EGR-1 mRNA, was exploited for gene silencing. All of the results of tumor treatment in vitro have implied that MnO2 -DNAzyme-TB nanocomposite (MDT) can internalize into cells. Subsequently, MDT could decrease the expression of EGR-1 by gene silencing that enabling inhibition of cell growth. In addition, the singlet oxygen which was generated by the aggregated TB were able to further suppress cell growth. Combination therapy of photodynamic as well as gene therapy greatly enhanced antitumor efficiencies. Furthermore, in vivo tumor treatment experiments demonstrated that MDT under illumination can effectively inhibit the tumor growth of MCF-7 tumor-bearing mice by photodynamic and gene silencing combination therapy.