文献类型：期刊文献

英文题名：Sequential Rocket-Mode Bioactivating Ticagrelor Prodrug Nanoplatform Combining Light-Switchable Diphtherin Transgene System for Breast Cancer Metastasis Inhibition

作者：Zou, Jiafeng[1,2,3];Sun, Rui[1];He, Muye[1];Chen, You[1];Cheng, Yi[1];Xia, Chuanhe[1];Ma, Ying[1];Zheng, Shulei[1];Fu, Xiuzhi[1];Yuan, Zeting[1,4];Lan, Minbo[2];Lou, Kaiyan[1,3];Chen, Xianjun[1,5,6,7];Gao, Feng[1,2,3,5,8]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[3]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[4]Shanghai Univ Tradit Chinese Med, Putuo Hosp, Intervent Canc Inst Chinese Integrat Med, Shanghai 200062, Peoples R China;[5]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[6]Chinese Acad Sci, Shanghai Inst Biol Sci, CAS Ctr Excellence Brain Sci, Shanghai 200031, Peoples R China;[7]Chinese Acad Med Sci, Res Unit New Tech Live Cell Metab Imaging, Beijing 100050, Peoples R China;[8]East China Univ Sci & Technol, Engn Res Ctr Pharmaceut Proc Chem, Sch Pharm, Minist Educ, Shanghai 200237, Peoples R China

年份：2023

卷号：15

期号：46

起止页码：53198

外文期刊名：ACS APPLIED MATERIALS & INTERFACES

收录：;EI(收录号：20234915156144);WOS:【SCI-EXPANDED(收录号:WOS:001108432400001)】；

基金：We thank Prof. Yuzheng Zhao (East China University of Science and Technology) and the Fundamental Research Funds for the Central Universities for the invaluable assistance of funding and equipment in this research. We also thank the Shanghai Municipal Education Commission-Frontier Research Base of Optogenetic Techniques for Cell Metabolism (to Y.Z.) and the State Key Laboratory of Bioreactor Engineering for providing several laboratory instruments. This work was supported by grants from the Development Program of China (Grant No. 2019YFA0904800 to Y.Z.), National Nature Science Foundation of China (Grant Nos. 32030065, 31722033, and 92049304 to Y.Z. and X.C.), Shanghai Sailing Program (Grant No. 21YF1410300 to F.G.), Science and Technology Commission of Shanghai Municipality (Grant No. 10DZ2220500 to F.G.), the Shanghai Committee of Science and Technology (Grant No. 11DZ2260600 to F.G.), Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, Grant 2021 Sci & Tech 03-28 to Y.Z. and X.C.), and the Research Unit of New Techniques for Live-Cell Metabolic Imaging (Chinese Academy of Medical Sciences, 2019-I2M-5-013 to Y.Z.).

语种：英文

外文关键词：breast cancer metastasis; LightOn system; ticagrelor; cell membrane fusionliposomes; sequential bioactivatingprodrug

摘要：The increased risk of breast cancer metastasis is closely linked to the effects of platelets. Our previously light-switchable diphtheria toxin A fragment (DTA) gene system, known as the LightOn system, has demonstrated significant therapeutic potential; it lacks antimetastatic capabilities. In this study, we devised an innovative system by combining cell membrane fusion liposomes (CML) loaded with the light-switchable transgene DTA (pDTA) and a ticagrelor (Tig) prodrug. This innovative system, named the sequential rocket-mode bioactivating drug delivery system (pDTA-Tig@CML), aims to achieve targeted pDTA delivery while concurrently inhibiting platelet activity through the sequential release of Tig triggered by reactive oxygen species with the tumor microenvironment. In vitro investigations have indicated that pDTA-Tig@CML, with its ability to sequentially release Tig and pDTA, effectively suppresses platelet activity, resulting in improved therapeutic outcomes and the mitigation of platelet driven metastasis in breast cancer. Furthermore, pDTA-Tig@CML exhibits enhanced tumor aggregation and successfully restrains tumor growth and metastasis. It also reduces the levels of ADP, ATP, TGF-beta, and P-selectin both in vitro and in vivo, underscoring the advantages of combining the bioactivating Tig prodrug nanoplatform with the LightOn system. Consequently, pDTA-Tig@CML emerges as a promising light-switchable DTA transgene system, offering a novel bioactivating prodrug platform for breast cancer treatment.