Exploiting the tumor microenvironment provides a new strategy for cancer treatment. In order to develop the microenvironment-selective photosensitiser, we rationally designed a proton-activatable aminated-chrysophanol derivative-compound 3, which combines fluorescence and reactive oxygen species regulated by the tumor acidic microenvironment for the first time. Furthermore, two PET tertiary amine substituents introduced by compound 3 enhance the cellular uptake, prolong the wavelength of the absorption, and increase the phototoxicity. Not only can compound 3 distinguish the cancer cells from normal cells but also the tumor from the normal tissue by the higher fluorescence intensity in cancer cells and tissues. Additionally, lysosome destruction test proves cell necrosis in lysosomal related pathway. We believe that the proton-activatable photosensitiser modulated by tumor acidic microenvironment offers a good chance for the cancer treatment in clinic.

开发肿瘤微环境为癌症治疗提供了新的策略。为了开发微环境选择性光敏剂，我们合理地设计了质子可活化的胺基-邻苯三酚衍生物3，该化合物首次结合了由肿瘤酸性微环境调节的荧光和活性氧。此外，由化合物3引入的两个PET叔胺取代基增强细胞吸收，延长吸收波长，并增加光毒性。化合物3不仅可以通过癌细胞和组织中较高的荧光强度，可以区分癌细胞和正常细胞，也可以区分肿瘤和正常组织。另外，溶酶体破坏试验证明了溶酶体相关途径中的细胞坏死。我们相信，由肿瘤酸性微环境调节的质子活化光敏剂为临床治疗癌症提供了很好的机会。