title: Cell-SELEX-based selection of aptamers that recognize distinct targets on metastatic colorectal cancer cells.
abstract: The development of diagnostic/therapeutic strategies against metastasis-related molecular targets is critical for improving the survival rate of cancer patients. Subtractive Cell-SELEX was performed using highly metastatic colorectal cancer (CRC) LoVo cells and non-metastatic HCT-8 cells as the target and negative cells, respectively, for the selection of metastatic-specific aptamers. This process generated seven aptamers that displayed highly specific binding to the target cells with Kds in the nanomolar range. Based on the distinct chemical/biological properties of their individual cell surface targets, the aptamers were separately functionalized: the receptor-targeting aptamer W14 was used as a carrier for doxorubicin, resulting in the specific delivery of the drug to the target cells and a significant reduction of its cytotoxicity to non-target cells, and the non-receptor-binding aptamer W3 was used as a molecular probe conjugated to quantum dots for the targeted imaging of metastatic cancer cell lines, spontaneous lung metastasis murine tissue, and metastatic CRC patient tissues. In addition, these aptamers can be used in combination due to their lack of detectable mutual-binding interference. The study demonstrates that a panel of aptamers that recognize distinct features of target molecules can be obtained through single Cell-SELEX selection, and the selected aptamers may be individually functionalized for specific applications and/or utilized in combination.
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, PR China.
authors.forename: Wan-Ming
authors.initials: WM
authors.lastname: Li
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun, Beijing 100190, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bing
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, PR China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Wei
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, PR China.
authors.forename: Zhe-Zhou
authors.initials: ZZ
authors.lastname: Chen
authors.affiliation: Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun, Beijing 100190, PR China. Electronic address: sgdh@iccas.ac.cn.
authors.forename: Di-Hua
authors.initials: DH
authors.lastname: Shangguan
authors.affiliation: Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 92 Beier Road, Heping District, Shenyang 110001, PR China. Electronic address: jfang61@netease.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D052157:Aptamers, Nucleotide / Q000737:chemistry*; D016466:CHO Cells; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D003412:Cricetulus; D003952:Diagnostic Imaging / Q000379:methods; D004317:Doxorubicin / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D015335:Molecular Probes; D041681:NIH 3T3 Cells; D045663:Quantum Dots; D052156:SELEX Aptamer Technique / Q000379:methods*
chemical_list: D052157:Aptamers, Nucleotide; D015335:Molecular Probes; D004317:Doxorubicin
keywords: Aptamer; Cell-SELEX; Drug delivery; Metastatic colorectal cancer; Molecular imaging; Quantum dots