Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate
作者全名："Xiang, Wei; Peng, Yongbo; Zeng, Hongliang; Yu, Chunping; Zhang, Qun; Liu, Biao; Liu, Jiahao; Hu, Xing; Wei, Wensu; Deng, Minhua; Wang, Ning; Liu, Xuewen; Xie, Jianfei; Hou, Weibin; Tang, Jin; Long, Zhi; Wang, Long; Liu, Jianye"
作者地址："[Xiang, Wei; Zeng, Hongliang; Liu, Biao; Liu, Jiahao; Hu, Xing; Hou, Weibin; Tang, Jin; Long, Zhi; Wang, Long; Liu, Jianye] Cent South Univ, Dept Onol, Xiangya Hosp 3, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China; [Peng, Yongbo] Chongqing Med Univ, Coll Pharm, Chongqing Key Lab Pharmaceut Metab Res, Key Lab Biochem & Mol Pharmacol, 1, Yixueyuan Rd, Chongqing 400016, Peoples R China; [Zeng, Hongliang] Hunan Acad Chinese Med, Inst Chinese Mat Med, 8, Yuehua Rd, Changsha 410013, Peoples R China; [Yu, Chunping; Wei, Wensu; Deng, Minhua; Wang, Ning] Sun Yat sen Univ, Dept Urol, Canc Ctr, 651 Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China; [Yu, Chunping; Wei, Wensu; Deng, Minhua; Wang, Ning] Collaborat Innovat Ctr Canc Med, State Key Lab Oncol Southern China, 651, Dongfeng Rd East, Guangzhou 510060, Guangdong, Peoples R China; [Zhang, Qun] Sun Yat sen Univ, Affiliated Hosp 1, Dept Radiotherapy, 58 Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China; [Xiang, Wei; Zeng, Hongliang; Liu, Biao; Liu, Jiahao; Hu, Xing; Hou, Weibin; Tang, Jin; Long, Zhi; Wang, Long; Liu, Jianye] Cent South Univ, Dept Urol, Xiangya Hosp 3, 138, Tongzipo Rd, Changsha 410013, Hunan, Peoples R China; [Xie, Jianfei] Cent South Univ, Dept Nursing, Xiangya Hosp 3, 138, Tongzipo Rd, Changsha 410013, Hunan, Peoples R China"
通信作者："Liu, JY (通讯作者)，Cent South Univ, Dept Onol, Xiangya Hosp 3, 138 Tongzipo Rd, Changsha 410013, Hunan, Peoples R China."
来源：BIOMATERIALS RESEARCH
ESI学科分类：
WOS号：WOS:000894439400003
JCR分区：Q1
影响因子：11.3
年份：2022
卷号：26
期号：1
开始页：
结束页：
文献类型：Article
关键词：Aptamer; PTK7; Bladder cancer; Targeted therapy; PTK7-GEMs
摘要："Background: Gemcitabine (GEM) is one of the first-line chemotherapies for bladder cancer (BC), but the GEMs cannot recognize cancer cells and have a low long-term response rate and high recurrence rate with side effects during the treatment of BC. Targeted transport of GEMs to mediate cytotoxicity to tumor and avoid the systemic side effects remains a challenge in the treatment of BC. Methods: Based on a firstly confirmed biomarker in BC-protein tyrosine kinase 7 (PTK7), which is overexpressed on the cell membrane surface in BC cells, a novel targeting system protein tyrosine kinase 7 aptamer-Gemcitabine conjugate (PTK7-GEMs) was designed and synthesized using a specific PTK7 aptamer and GEM through auto-synthesis method to deliver GEM against BC. In addition, the antitumor effects and safety evaluation of PTK7-GEMs was assessed with a series of in vitro and in vivo assays. Results: PTK7-GEMs can specifically bind and enter to BC cells dependent on the expression levels of PTK7 and via the macropinocytosis pathway, which induced cytotoxicity after GEM cleavage from PTK7-GEMs respond to the intracellular phosphatase. Moreover, PTK7-GEMs showed stronger anti-tumor efficacy and excellent biosafety in three types of tumor xenograft mice models. Conclusion: These results demonstrated that PTK7-GEMs is a successful targeted aptamer-drug conjugates strategy (APDCs) to treat BC, which will provide new directions for the precision treatment of BC in the field of biomarker-oriented tumor targeted therapy."
基金机构：Huxiang Young Talents Plan Project of Hunan Province; Hunan High-tech Industry Science and Technology Innovation Leading Plan [2019RS2015]; Bethune Special Research Fund Project of Urological Oncology [2020SK2012]; [mnzl202030]; [mnzl202006]
基金资助正文："This work was supported by Huxiang Young Talents Plan Project of Hunan Province (2019RS2015), Hunan High-tech Industry Science and Technology Innovation Leading Plan (2020SK2012), and Bethune Special Research Fund Project of Urological Oncology (mnzl202030, mnzl202006)"
