Citation: DING Pi, DING Zi-Xin, MA Jia-Ling, ZHOU Tong-Ping, PAN Yue, HU Ming-Chao, WANG Zhi-Li, SUN Na, PEI Ren-Jun. Effective Isolation, Label and Release of Multitype Circulating Tumor Cells Base on CdSe/ZnS Quantum Dots and Dual-antibody Modified Magnetic Nanoparticles[J]. Chinese Journal of Analytical Chemistry, ;2023, 51(5): 821-832. doi: 10.19756/j.issn.0253-3820.221642 shu

Effective Isolation, Label and Release of Multitype Circulating Tumor Cells Base on CdSe/ZnS Quantum Dots and Dual-antibody Modified Magnetic Nanoparticles

DING Pi ¹ ,
DING Zi-Xin ^1,2 ,
MA Jia-Ling ^1,3 ,
ZHOU Tong-Ping ^1,3 ,
PAN Yue ^1,3 ,
HU Ming-Chao ^1,3 ,
WANG Zhi-Li ^1,, ,
SUN Na ^1,, ,
PEI Ren-Jun ¹

1.
Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou 215123, China;
2.
Center of Advanced Pharmaceuticals and Biomaterials, State Key Laboratory of Natural Medcines, China Pharmaceutical University, Nanjing 210009, China;
3.
The Second Affiliated Hospital of Soochow University, Suzhou 215004, China

Corresponding author: WANG Zhi-Li, SUN Na,
Received Date: 19 December 2022
Revised Date: 4 March 2023

Fund Project: Supported by the National Natural Science Foundation of China (No. 32000984) and the Natural Science Foundation of Jiangsu Province, China (Nos. BK20220099, BE2021665).

The identification and dynamic monitoring of circulating tumor cells (CTCs) are of vital importance for clinical diagnosis, prognosis evaluation and personalized therapy of cancer patients. However, during the process of tumor metastasis, epithelial-mesenchymal transition (EMT) may occur, resulting in the loss of the expression of surface protein markers on tumor cells, which makes it difficult to effectively isolate CTCs using traditional enrichment strategies based on a single epithelial characteristic marker. In addition, the immunostaining methods commonly used to identify CTCs require cell fixation, which can only provide limited information on the number of CTCs, thus limiting further biological research on CTCs. To address these issues, this study prepared magnetite nanoparticles (MNPs) with a core-shell structure to enable enrichment, purification and identification of different types of CTCs. The outer layer was decorated with CdSe/ZnS quantum dots (QDs) to enable labeling, while the subsequently modified gelatin layer could suppress non-specific adhesion of blood cells with good performance of thermos-sensitivity for CTC release. Finally, two types of antibodies targeting epithelial cell adhesion molecule (EpCAM) and N-cadherin were modified on the surface of MNPs, creating a simple and efficient platform for CTCs enrichment, labeling and release. The capture efficiency of the platform for epithelial and mesenchymal CTCs reached 85.5% and 92.4%, respectively. In addition, the layer of QDs assembled on the surface of MNPs enabled labeling and identification of target cells without cell fixation and immune-staining processes. After a short time of incubation at 37 ℃, 88% of the captured cells were successfully released due to the conformation change of gelatin molecules on the surface of MNPs, with a cell viability of 94.9%. The platform developed here provided a new strategy for CTC detection in clinical application.
- Circulating tumor cells,
- Gelatin,
- Fluorescent labeling,
- Enrichment,
- Isolation
1. [1]
  WILLIAMS S C P. Proc. Natl. Acad. Sci. U. S. A., 2013, 110(13):4861.
2. [2]
  THIELE J A, BETHEL K, KRÁLÍČKOVÁ M, KUHN P. Annu. Rev. Pathol. Mech. Dis., 2017, 12(1):419-447.
3. [3]
  LIN E, CAO T, NAGRATH S, KING M R. Annu. Rev. Biomed. Eng., 2018, 20(1):329-352.
4. [4]
  CASTRO-GINER F, ACETO N. Genome Med., 2020, 12(1):31.
5. [5]
  AHN J C, TENG P, CHEN P, POSADAS E, TSENG H, LU S C, YANG J D. Hepatology, 2021, 73(1):422-436.
6. [6]
  LALLO A, SCHENK M W, FRESE K K, BLACKHALL F, DIVE C. Transl. Lung Cancer Res., 2017, 6(4):397-408.
7. [7]
  RAO L, MENG Q F, HUANG Q, WANG Z, YU G T, LI A, MA W, ZHANG N, GUO S S, ZHAO X Z, LIU K, YUAN Y, LIU W. Adv. Funct. Mater., 2018, 28(34):1803531.
8. [8]
  DONG J, CHEN J F, SMALLEY M, ZHAO M, KE Z, ZHU Y, TSENG H. Adv. Mater., 2020, 32(1):1903663.
9. [9]
  LI W, LI R, HUANG B, WANG Z X, SUN Y, WEI X Y, HENG C, LIU W, YU M X, GUO S S, ZHAO X Z. Nanotechnology, 2019, 30(33):335201.
10. [10]
  PARK G S, KWON H, KWAK D W, PARK S Y, KIM M, LEE J H, HAN H, HEO S, LI X S, LEE J H, KIM Y H, LEE J G, YANG W, CHO H Y, KIM S K, KIM K. Nano Lett., 2012, 12(3):1638-1642.
11. [11]
  ZHANG N, DENG Y, TAI Q, CHENG B, ZHAO L, SHEN Q, HE R, HONG L, LIU W, GUO S, LIU K, TSENG H R, XIONG B, ZHAO X Z. Adv. Mater., 2012, 24(20):2756-2760.
12. [12]
  ABDOLAHAD M, TAGHINEJAD M, TAGHINEJAD H, JANMALEKI M, MOHAJERZADEH S. Lab Chip, 2012, 12(6):1183-1190.
13. [13]
  ZHANG P, CHEN L, XU T, LIU H, LIU X, MENG J, YANG G, JIANG L, WANG S. Adv. Mater., 2013, 25(26):3566-3570.
14. [14]
  CHEN W, WENG S, ZHANG F, ALLEN S, LI X, BAO L, LAM R H W, MACOSKA J A, MERAJVER S D, FU J. ACS Nano, 2013, 7(1):566-575.
15. [15]
  STOTT S L, HSU C H, TSUKROV D I, YU M, MIYAMOTO D T, WALTMAN B A, ROTHENBERG S M, SHAH A M, SMAS M E, KORIR G K, FLOYD JR. F P, GILMAN A J, LORD J B, WINOKUR D, SPRINGER S, IRIMIA D, NAGRATH S, SEQUIST L V, LEE R J, ISSELBACHER K J, MAHESWARAN S, HABER D A, TONER M. Proc. Natl. Acad. Sci. U. S. A., 2010, 107(43):18392-18397.
16. [16]
  WANG S, WANG H, JIAO J, CHEN K J, OWENS G E, KAMEI K, SUN J, SHERMAN D J, BEHRENBRUCH C P, WU H, TSENG H R. Angew. Chem. Int. Ed., 2009, 48(47):8970-8973.
17. [17]
  SHI F, JIA F, WEI Z, MA Y, FANG Z, ZHANG W, HU Z. Proteomics, 2021, 21(3-4):2000060.
18. [18]
  ZHANG C, GUAN Y, SUN Y, AI D, GUO Q. Cancer Lett., 2016, 374(2):216-223.
19. [19]
  ALIX-PANABIÈRES C, MADER S, PANTEL K. J. Mol. Med., 2017, 95(2):133-142.
20. [20]
  JOU H J, LING P Y, HSU H T. Taiwan. J. Obstet. Gynecol., 2022, 61(1):34-39.
21. [21]
  LI Q, ZHI X, ZHOU J, TAO R, ZHANG J, CHEN P, RØE O D, SUN L, MA L. Oncotarget, 2016, 7(24):36645-36654.
22. [22]
  QAYYUMI B, BHARDE A, ALAND G, D'SOUZA A, JAYANT S, SINGH N, TRIPATHI S, BADAVE R, KALE N, SINGH B, ARORA S, GORE I, SINGH A, VASUDEVAN A, PRABHASH K, KHANDARE J, CHATURVEDI P. Oral Surg., Oral Med., Oral Pathol., 2022, 134(1):73-83.
23. [23]
  MESSARITAKIS I, POLITAKI E, KOTSAKIS A, DERMITZAKI E K, KOINIS F, LAGOUDAKI E, KOUTSOPOULOS A, KALLERGI G, SOUGLAKOS J, GEORGOULIAS V. PLoS One, 2017, 12(7):e0181211.
24. [24]
  SONG H, SU Y, ZHANG L, LV Y. Luminescence, 2019, 34(6):530-543.
25. [25]
  PLESKOVA S, MIKHEEVA E, GORNOSTAEVA E. Adv. Exp. Med. Biol., 2018, 1048:323-334.
26. [26]
  GUO X, WU Z, LI W, WANG Z, LI Q, KONG F, ZHANG H, ZHU X, DU Y P, JIN Y, DU Y, YOU J. ACS Appl. Mater. Interfaces, 2016, 8(5):3092-3106.
1. [1]
  Wei Huang , Weiwei Chen , Yongxing Tang . Green Mountains and Blue Waters Spanning Nine Centuries: Decrypting “The Picture of a Thousand Miles of Rivers and Mountains” from a Chemical Perspective. University Chemistry, 2024, 39(9): 189-195. doi: 10.12461/PKU.DXHX202312075
2. [2]
  Xinyi Hong , Tailing Xue , Zhou Xu , Enrong Xie , Mingkai Wu , Qingqing Wang , Lina Wu . Non-Site-Specific Fluorescent Labeling of Proteins as a Chemical Biology Experiment. University Chemistry, 2024, 39(4): 351-360. doi: 10.3866/PKU.DXHX202310010
3. [3]
  Siyi ZHONG , Xiaowen LIN , Jiaxin LIU , Ruyi WANG , Tao LIANG , Zhengfeng DENG , Ao ZHONG , Cuiping HAN . Targeting imaging and detection of ovarian cancer cells based on fluorescent magnetic carbon dots. Chinese Journal of Inorganic Chemistry, 2024, 40(8): 1483-1490. doi: 10.11862/CJIC.20240093
4. [4]
  Zhaoxin LI , Ruibo WEI , Min ZHANG , Zefeng WANG , Jing ZHENG , Jianbo LIU . Advancements in the construction of inorganic protocells and their cell mimic and bio-catalytical applications. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2286-2302. doi: 10.11862/CJIC.20240235
5. [5]
  Shuyu Liu , Xiaomin Sun , Bohan Song , Gaofeng Zeng , Bingbing Du , Chongshen Guo , Cong Wang , Lei Wang . Design and Fabrication of Phospholipid-Vesicle-based Artificial Cells towards Biomedical Applications. University Chemistry, 2024, 39(11): 182-188. doi: 10.12461/PKU.DXHX202404113
6. [6]
  Shanying Chen , Kangning Huo , Ke Qi , Jingyi Li , Shuxin Li , Yunchao Li . A Novel Colloid Electrophoresis Experiment with the Characteristics of Resource Recycling and Inquiry-Driven Experimental Design. University Chemistry, 2024, 39(5): 274-286. doi: 10.3866/PKU.DXHX202311067
7. [7]
  Shipeng WANG , Shangyu XIE , Luxian LIANG , Xuehong WANG , Jie WEI , Deqiang WANG . Piezoelectric effect of Mn, Bi co-doped sodium niobate for promoting cell proliferation and bacteriostasis. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1919-1931. doi: 10.11862/CJIC.20240094
8. [8]
  Aiai WANG , Lu ZHAO , Yunfeng BAI , Feng FENG . Research progress of bimetallic organic framework in tumor diagnosis and treatment. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1825-1839. doi: 10.11862/CJIC.20240225
9. [9]
  Peng GENG , Guangcan XIANG , Wen ZHANG , Haichuang LAN , Shuzhang XIAO . Hollow copper sulfide loaded protoporphyrin for photothermal-sonodynamic therapy of cancer cells. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1903-1910. doi: 10.11862/CJIC.20240155
10. [10]
  Tingting XU , Wenjing ZHANG , Yongbo SONG . Research advances of atomic precision coinage metal nanoclusters in tumor therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2275-2285. doi: 10.11862/CJIC.20240229
11. [11]
  Jian Li , Yu Zhang , Rongrong Yan , Kaiyuan Sun , Xiaoqing Liu , Zishang Liang , Yinan Jiao , Hui Bu , Xin Chen , Jinjin Zhao , Jianlin Shi . 高效靶向示踪钙钛矿纳米系统光电增效抗肿瘤. Acta Physico-Chimica Sinica, 2025, 41(5): 100042-. doi: 10.1016/j.actphy.2024.100042
12. [12]
  Donghui PAN , Yuping XU , Xinyu WANG , Lizhen WANG , Junjie YAN , Dongjian SHI , Min YANG , Mingqing CHEN . Preparation and in vivo tracing of ⁶⁸Ga-labeled PM_2.5 mimetic particles for positron emission tomography imaging. Chinese Journal of Inorganic Chemistry, 2024, 40(4): 669-676. doi: 10.11862/CJIC.20230468
13. [13]
  Zhicheng JU , Wenxuan FU , Baoyan WANG , Ao LUO , Jiangmin JIANG , Yueli SHI , Yongli CUI . MOF-derived nickel-cobalt bimetallic sulfide microspheres coated by carbon: Preparation and long cycling performance for sodium storage. Chinese Journal of Inorganic Chemistry, 2025, 41(4): 661-674. doi: 10.11862/CJIC.20240363
14. [14]
  Yan ZHAO , Xiaokang JIANG , Zhonghui LI , Jiaxu WANG , Hengwei ZHOU , Hai GUO . Preparation and fluorescence properties of Eu³⁺-doped CaLaGaO₄ red-emitting phosphors. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1861-1868. doi: 10.11862/CJIC.20240242
15. [15]
  Di WU , Ruimeng SHI , Zhaoyang WANG , Yuehua SHI , Fan YANG , Leyong ZENG . Construction of pH/photothermal dual-responsive delivery nanosystem for combination therapy of drug-resistant bladder cancer cell. Chinese Journal of Inorganic Chemistry, 2024, 40(9): 1679-1688. doi: 10.11862/CJIC.20240135
16. [16]
  Ping Song , Nan Zhang , Jie Wang , Rui Yan , Zhiqiang Wang , Yingxue Jin . Experimental Teaching Design on Synthesis and Antitumor Activity Study of Cu-Pyropheophorbide-a Methyl Ester. University Chemistry, 2024, 39(6): 278-286. doi: 10.3866/PKU.DXHX202310087
17. [17]
  Jiahui CHEN , Tingting ZHENG , Xiuyun ZHANG , Wei LÜ . Research progress of near-infrared absorption inorganic nanomaterials in photothermal and photodynamic therapy of tumors. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2396-2414. doi: 10.11862/CJIC.20240106
18. [18]
  Jing WU , Puzhen HUI , Huilin ZHENG , Pingchuan YUAN , Chunfei WANG , Hui WANG , Xiaoxia GU . Synthesis, crystal structures, and antitumor activities of transition metal complexes incorporating a naphthol-aldehyde Schiff base ligand. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2422-2428. doi: 10.11862/CJIC.20240278
19. [19]
  Xinyu Liu , Weiran Hu , Zhengkai Li , Wei Ji , Xiao Ni . Algin Lab: Surging Luminescent Sea. University Chemistry, 2024, 39(5): 396-404. doi: 10.3866/PKU.DXHX202312021
20. [20]
  Jie WU , Zhihong LUO , Xiaoli CHEN , Fangfang XIONG , Li CHEN , Biao ZHANG , Bin SHI , Quansheng OUYANG , Jiaojing SHAO . Critical roles of AlPO₄ coating in enhancing cycling stability and rate capability of high voltage LiNi_0.5Mn_1.5O₄ cathode materials. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 948-958. doi: 10.11862/CJIC.20240400

Get Citation

PDF

XML

Metrics

PDF Downloads(11)
Abstract views(1732)
HTML views(99)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142