摘要
肿瘤细胞的转移性和异质性,以及肿瘤内环境的复杂多变,给肿瘤检测造成了极大困难。建立准确的肿瘤检测方法对其有效诊疗意义重大。与普通细胞相比,快速增殖的肿瘤细胞通常需要高表达特定酶,例如HeLa细胞中磷酸酶就是处于高表达状态。基于肿瘤细胞的这一特点,本报告阐述了一种利用酶催化来实现超分子自组装的策略,使得自组装不但能够在活体内形成,而且可以准确区分普通细胞和肿瘤细胞,正常组织与肿瘤病灶。首先我们在体外发展了一类基于多肽的超分子自组装体系,在磷酸酶催化作用下可以有效形成纳米自组装体。其次,确认了在HeLa细胞内超分子自组装发生于内质网的现象,这一点与磷酸酶集中分布于内质网表面相呼应。此外,我们在荷瘤小鼠模型上也实现了超分子自组装,并通过有效调控吲哚菁綠(ICG)在小鼠体内的时空分布,使得ICG特异性地在肿瘤内蓄积,由此为活体内肿瘤的诊断治疗提供了一种新方法。
It is crucial to develop effective and precise method for tumor diagnosis in vivo.According to the over-expressed enzyme activity in tumor cells,here we verified the enzyme instructed supramolecular self-assembly strategy in vivo.Our self-assembly system was based on a series of peptide derivative and owned the capability to distinct the cancer cells from normal cells,and tumor from normal tissues as well.In cell level,we confirmed that the supramolecular self-assembly occurred on endoplasmic reticulum due to the pronounced phosphatase activity.Further,we found that the supramolecular self-assembly can specifically accumulate therapeutic agent inside tumor on a mouse model.The manipulation the spatiotemporal distribution of therapeutic agent by our self-assembly system revealed its potential for better tumor theranostics.
引文
[1]Gao,Y.;Shi,J.F.;Yuan,D.;Xu,B.*Nat.Commun.,2012,3,1033.
[2]Gao,Y.;Berciu,C.;Kuang,Y.;Shi,J.F.;Nicastro,D.;Xu,B.*ACS Nano,2013,7,9055.
[3]Huang,P.*,Gao,Y*,et al.ACS Nano,2015,9,9517.