Dually stimulative single-chain polymeric nano lock with dynamic ligands for sensitive detection of circulating tumor cells

作者全名："Cui, Miao; Chen, Xiaoyu; Luo, Xu; Zhou, Zhihang; Chen, Zhiji; Zhou, Zhengdong; Zhou, Xiaoyu; Zou, Heng; Xu, Tao; Wang, Shubin; Yang, Mengsu"

作者地址："[Cui, Miao] Shenzhen Bay Lab, Shenzhen 518132, Peoples R China; [Cui, Miao; Zhou, Zhihang; Zhou, Zhengdong; Zhou, Xiaoyu; Zou, Heng; Xu, Tao; Yang, Mengsu] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China; [Cui, Miao; Zhou, Zhihang; Zhou, Zhengdong; Zhou, Xiaoyu; Zou, Heng; Xu, Tao; Yang, Mengsu] City Univ Hong Kong, Tung Biomed Sci Ctr, Hong Kong, Peoples R China; [Cui, Miao; Luo, Xu; Zhou, Xiaoyu; Yang, Mengsu] City Univ Hong Kong, Shenzhen Res Inst, Biotech & Hlth Ctr, Key Lab Biochip Technol, Shenzhen 518057, Peoples R China; [Chen, Xiaoyu] MIT, Dept Mech Engn, Cambridge, MA 02139 USA; [Zhou, Zhihang; Chen, Zhiji] Chongqing Med Univ, Affiliated Hosp 2, Dept Gastroenterol, Chongqing 400016, Peoples R China; [Zou, Heng; Xu, Tao] Cell Shenzhen Ltd, Shenzhen, Peoples R China; [Wang, Shubin] Peking Univ, Shenzhen Hosp, Canc Inst, Dept Oncol,Shenzhen Key Lab Gastrointestinal Canc, Shenzhen 518036, Peoples R China"

通信作者："Cui, M (通讯作者)，Shenzhen Bay Lab, Shenzhen 518132, Peoples R China.; Cui, M; Yang, MS (通讯作者)，City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China.; Cui, M; Yang, MS (通讯作者)，City Univ Hong Kong, Tung Biomed Sci Ctr, Hong Kong, Peoples R China."

来源：BIOSENSORS & BIOELECTRONICS

ESI学科分类：CHEMISTRY

WOS号：WOS:000863559900006

JCR分区：Q1

影响因子：12.6

年份：2022

卷号：217

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Single-chain nano lock; Surface sialic acid; Broad-spectrum cancer type; CTCs detection; Metastasis assessment

摘要："Circulating tumor cells (CTCs) are important markers for cancer diagnosis and monitoring. However, CTCs detection remains challenging due to their scarcity, where most of the detection methods are compromised by the loss of CTCs in pre-enrichment, and by the lack of universal antibodies for capturing different kinds of cancer cells. Herein, we report a single-chain based nano lock (SCNL) polymer incorporating dually stimulative dynamic ligands that can bind with a broad spectrum of cancer cells and CTCs overexpressing sialic acid (SA) with high sensitivity and selectivity. The high sensitivity is realized by the polymeric single chain structure and the multi-valent functional moieties, which improve the accessibility and binding stability between the target cells and the SCNL. The highly selective targeting of cancer cells is achieved by the dynamic and dually stimulative nano lock structures, which can be unlocked and functionalized upon simultaneous exposure to overexpressed SA and acidic microenvironment. We applied the SCNL to detecting cancer cells and CTCs in clinical samples, where the detection threshold of SCNL reached 4 cells/mL. Besides CTCs enumeration, the SCNL approach could also be extended to metastasis assessment through monitoring the expressing level of surface SA on cancer cells."

基金机构："National Key Research and Development Program of China [2018YFA0901104]; Hong Kong Research Grant Council [CityU_11319516, R102018F]; Guangdong Provincial Science and Technology Project [2017B020226001]; Basic Research Project of Shenzhen Knowledge Innovation Program [JCYJ20170818095453642, JCYJ20180307123759162]; Guangdong Medical Science and Technology Research Fund [2019116154356500]; Guangdong Basic and Applied Basic Research Foundation, Shenzhen Joint Fund, Youth Fund Project 2019 [2019A1515111207]"

基金资助正文："We are grateful for Dr. Yihan Jing. This research is supported by the Guangdong Basic and Applied Basic Research Foundation, Shenzhen Joint Fund, Youth Fund Project 2019 (2019A1515111207), the National Key Research and Development Program of China (2018YFA0901104), the Hong Kong Research Grant Council (CityU_11319516 and R102018F), the Guangdong Provincial Science and Technology Project (2017B020226001), and the Basic Research Project of Shenzhen Knowledge Innovation Program (JCYJ20170818095453642 and JCYJ20180307123759162). The work described in this paper is also partially supported by Guangdong Medical Science and Technology Research Fund (2019116154356500)."