DataVXBiomaterials ResearchPaper
journal article·2022-09-30Open access

Targeting treatment of bladder cancer using PTK7 aptamer-gemcitabine conjugate

Wei Xiang, Yongbo Peng, Hongliang Zeng, Chunping Yu, Qun Zhang, Biao Liu, Jiahao Liu, Xing Hu, Wensu Wei, Minhua Deng, Ning Wang, Xuewen Liu, Jianfei Xie, Weibin Hou, Jin Tang, Zhi Long, Long Wang, Jianye Liu

Biomaterials Research· Volume 26· Issue 1
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Abstract

Abstract 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.
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Research context

OpenAlex topics: Protein Tyrosine Phosphatases · HER2/EGFR in Cancer Research · Protease and Inhibitor Mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Urology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha 410013, Hunan, China.

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.

Institute of Chinese Materia Medica, Hunan Academy of Chinese Medicine, No.8, Yuehua Road, Changsha 410013, China.

Department of Urology, Sun Yat-sen University Cancer Center, No. 651, Dongfeng Road East, Guangzhou 510060, Guangdong, China.

State Key Laboratory of Oncology in Southern China, Collaborative Innovation Center for Cancer Medicine, No. 651, Dongfeng Road East, Guangzhou 510060, Guangdong, China.

Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, 58 Zhongshan 2nd Road, Guangzhou 510080, Guangdong, China.

Department of Onology, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha 410013, Hunan, China.

Department of Nursing, The Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Changsha 410013, Hunan, China.

Funding

Huxiang Young Talents Plan Project of Hunan Province · Hunan High-tech Industry Science and Technology Innovation Leading Plan · Bethune Special Research Fund Project of Urological Oncology

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