Li Yanhua, Zhao Jiexiang, Tang Kun, Yin Jiaqi, Song Yingying, Pan Wei, Li Na, Tang Bo
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan, 250014, PR China.
College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan, 250014, PR China.
Biosens Bioelectron. 2025 Mar 15;272:117127. doi: 10.1016/j.bios.2025.117127. Epub 2025 Jan 2.
The γ-glutamyl transpeptidase (γ-GGT) is an important tumor marker, which has been reported to be firmly associated with the developmental stage of liver cancer. Therefore, it makes sense to image and monitor γ-GGT level and design γ-GGT-responsive prodrug for integrated diagnosis and treatment of liver cancer. Herein, we prepare a doxorubicin (Dox) prodrug for imaging γ-GGT and on-demand treating liver cancer. When γ-GGT exists, the γ-glutamyl group will be cut off to liberate free Dox for monitoring cancer progression and killing tumor cells. Fortunately, little Dox is released due to the low level of γ-GGT in normal cells, which improves the safety and efficiency of chemotherapy. To further improve the tumor targeted ability, Dox prodrug is loaded in hyaluronic acid modified liposome nanoparticles to form the nano-prodrug. Then nano-prodrug is enriched in the tumor by binding to the high expressed CD44 on cancer cells. With the assistance of anti-PD-L1, nano-prodrug effectively inhibits the growth of proximal and distal tumors.
γ-谷氨酰转肽酶（γ-GGT）是一种重要的肿瘤标志物，据报道它与肝癌的发展阶段密切相关。因此，对γ-GGT水平进行成像和监测，并设计γ-GGT响应性前药用于肝癌的综合诊断和治疗是有意义的。在此，我们制备了一种用于γ-GGT成像和按需治疗肝癌的阿霉素（Dox）前药。当存在γ-GGT时，γ-谷氨酰基将被切断以释放游离的Dox，用于监测癌症进展和杀死肿瘤细胞。幸运的是，由于正常细胞中γ-GGT水平较低，释放的Dox很少，这提高了化疗的安全性和效率。为了进一步提高肿瘤靶向能力，将Dox前药负载于透明质酸修饰的脂质体纳米粒中形成纳米前药。然后纳米前药通过与癌细胞上高表达的CD44结合而富集于肿瘤中。在抗PD-L1的辅助下，纳米前药有效抑制近端和远端肿瘤的生长。
