Zhu Wei-Jin, Niu Jin-Yun, Sun Ru, Xu Yu-Jie, Ge Jian-Feng
College of Chemistry, Chemical Engineering and Material Science, Soochow University, Suzhou 215123, PR China.
State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow University, Suzhou 215123, PR China.
Bioorg Med Chem Lett. 2018 Sep 15;28(17):2953-2956. doi: 10.1016/j.bmcl.2018.07.004. Epub 2018 Jul 5.
In order to improve lysosome targetability of probes, fluorescent probes based on benzo[a]phenoxazine attaching different length oligoethyleneoxy chains were designed and prepared. Probes 2a-c containing N-pyridineium-3-yl exhibited almost ON-OFF near-infrared emission responses at 697-701 nm from pH 2.8 to 7.2, and the calculated pK values of 2a-c were 4.90, 4.92 and 5.03 respectively. More importantly, fluorescent imaging experiments indicated that probes 2a-c were all lysosome biomarkers for Ges-1 and HeLa cells, which was because the introduction of oligoethyleneoxy groups improved the biocompatibility of probes, so that the probes 2a-c were better transported to lysosomes via the endocytosis pathway of the cells. Moreover, the probe 2a was selected as a representative, which not only showed good reversibility and selectivity, but used to successfully image lysosomal pH increases induced by chloroquine.
为了提高探针的溶酶体靶向性，设计并制备了基于苯并[a]吩恶嗪并连接不同长度聚乙二醇氧链的荧光探针。含有N-吡啶鎓-3-基的探针2a-c在pH 2.8至7.2范围内于697-701 nm处表现出几乎开-关型近红外发射响应，且2a-c的计算pK值分别为4.90、4.92和5.03。更重要的是，荧光成像实验表明探针2a-c均为Ges-1和HeLa细胞的溶酶体生物标志物，这是因为聚乙二醇氧基的引入提高了探针的生物相容性，使得探针2a-c能够通过细胞的内吞途径更好地转运至溶酶体。此外，选择探针2a作为代表，其不仅表现出良好的可逆性和选择性，还成功用于成像由氯喹诱导的溶酶体pH升高。
