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Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

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机构： [1]Department of Urology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha, Hunan, 410013, China. [2]Chongqing Key Laboratory for Pharmaceutical Metabolism Research, the Key Laboratory of Biochemistry and Molecular Pharmacology, College of Pharmacy, Chongqing Medical University, No.1, Yixueyuan Road, Chongqing, 400016, China. [3]Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, No.8, Yuehua Road, Changsha, 410013, China. [4]Department of Urology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou, Guangdong, 510060, China. [5]State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road East, Guangzhou, Guangdong, 510060, China. [6]Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou, Guangdong, 510080, China. [7]Department of Onology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha, Hunan, 410013, China. [8]Department of Nursing, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha, Hunan, 410013, China.

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关键词： Aptamer PTK7 Bladder cancer Targeted therapy PTK7-GEMs

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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.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.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.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.© 2022. The Author(s).

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大类 | 2 区医学

小类 | 2 区工程：生物医学 2 区材料科学：生物材料

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Q1 ENGINEERING, BIOMEDICAL Q1 MATERIALS SCIENCE, BIOMATERIALS

影响因子： 8.1 最新[2023版] 0 最新五年平均 0 出版当年[2020版] 0 出版当年五年平均 0 出版前一年[2019版] 15.863 出版后一年[2021版]

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第一作者机构： [1]Department of Urology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha, Hunan, 410013, China.

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