Wu Dan, Song Guofen, Li Zhi, Zhang Tao, Wei Wei, Chen Muzi, He Xuewen, Ma Nan
The Key Lab of Health Chemistry and Molecular Diagnosis of Suzhou College of Chemistry , Chemical Engineering and Materials Science , Soochow University , 199 Ren'ai Road , Suzhou , 215123 , P. R. China . Email:
Chem Sci. 2015 Jul 1;6(7):3839-3844. doi: 10.1039/c4sc03894k. Epub 2015 Apr 8.
Ideal theranostics should possess directly correlated imaging and therapy modalities that could be simultaneously activated in the disease site to generate high imaging contrast and therapeutic efficacy with minimal side effects. However, so far it still remains challenging to engineer all these characteristics into a single theranostic probe. Herein, we report a new type of photosensitizer (PS)-derived "two-dimensional" molecular beacon (TMB) that could be specifically activated within tumor cells to exhibit both high imaging contrast and therapeutic efficacy that outperforms conventional photosensitizers for cancer theranostics. The TMB is constructed by integrating a photosensitizer (chlorin e6 (Ce6)), a quantum dot (QD), and a dark quencher (BHQ3) into a hairpin DNA molecule to generate multiple synergistic FRET modes. The imaging modality and therapy modality, which are mediated by FRET between the QD and BHQ3 and FRET between the QD and Ce6 respectively, are interconnected within the TMB and could be simultaneously activated by tumor mRNA molecules. We show that highly effective cancer imaging and therapy could be achieved for cancer cell lines and xenografted tumor models. The reported TMB represents an unprecedented theranostic platform for intelligent cancer theranostics.
理想的诊疗一体化试剂应具备直接相关的成像和治疗方式，能够在疾病部位同时被激活，以产生高成像对比度和治疗效果，且副作用最小。然而，迄今为止，将所有这些特性整合到单个诊疗一体化探针中仍然具有挑战性。在此，我们报道了一种新型的源自光敏剂（PS）的“二维”分子信标（TMB），它可以在肿瘤细胞内被特异性激活，展现出高成像对比度和治疗效果，在癌症诊疗方面优于传统光敏剂。TMB是通过将一种光敏剂（二氢卟吩e6（Ce6））、一个量子点（QD）和一个暗猝灭剂（BHQ3）整合到一个发夹DNA分子中构建而成，以产生多种协同荧光共振能量转移（FRET）模式。成像模式和治疗模式分别由QD与BHQ3之间的FRET以及QD与Ce6之间的FRET介导，在TMB内部相互关联，并且可以被肿瘤mRNA分子同时激活。我们表明，对于癌细胞系和异种移植肿瘤模型，可以实现高效的癌症成像和治疗。所报道的TMB代表了一种用于智能癌症诊疗的前所未有的诊疗一体化平台。
