journal article·2017-12-26

Biostable Aptamer Rings Conjugated for Targeting Two Biomarkers on Circulating Tumor Cells in Vivo with Great Precision

Haiyan Dong, Longyu Han, Zai-Sheng Wu, Ting Zhang, Jingjing Xie, Ji Ma, Jie Wang, Tao Li, Yu Gao, Jingwei Shao, Patrick J. Sinko, Lee Jia

Chemistry of Materials· Volume 29· Issue 24
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Abstract

Cancer metastatic spread is life-threatening and caused by circulating tumor cells (CTCs) that are very difficult to precisely capture in vivo. Here we show that two aptamer rings targeting different CTC biomarker epitopes conjugated on dendrimers capture CTCs with enhanced precision even in the presence of 10 8 interfering cells, or blood cells, and in mice or patient samples when compared with their single aptamer counterparts. The aptamer-conjugate inhibited in vivo metastasis and demonstrated enhanced biostability by resisting biodegradation caused by the endogenous nucleases. The capture arms of the aptamer conjugates could simultaneously and specifically seize two biomarkers (EpCAM and Her2). The double seizure resulted in significant cell-cycle arrest, apoptosis, and growth inhibition of the captured CTCs. The aptamer-conjugate highly penetrated and accumulated in mouse tumors. This study provides the first conceptual evidence that two aptamer rings, inexpensive but bioequivalent to their antibodies, can be biocompatibly conjugated to specifically capture and down-regulate CTCs in vivo with the enhanced biostability.
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Research context

OpenAlex topics: Advanced biosensing and bioanalysis techniques · RNA Interference and Gene Delivery · Immunotherapy and Immune Responses

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

Affiliations

Cancer Metastasis Alert and Prevention Centre and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, Fuzhou University, Fuzhou, Fujian 350002, China

Fujian Key Laboratory for Translational Research in Cancer and Neurodegenerative Diseases Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian 350108, China

Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, Fujian 350108, China

School of Pharmaceutical Sciences and Fujian Provincial Key Laboratory of Innovative Drug Target Research, Xiamen University, Xiang’an South Road, Xiamen, Fujian 361102, China

Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8020, United States

Funding

Ministry of Science and Technology of the People's Republic of China · Natural Science Foundation of Fujian Province · National Natural Science Foundation of China · Principal Fund, Xiamen University · Fujian Provincial Development And Reform Commission

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