Citation: Jing Huang, Danyang Wang, Shuhua Li, Hong Fan, Louzhen Fan. Red Fluorescent Carbon Quantum Dots for Diagnosis of Acidic Microenvironment in Tumors[J]. Acta Physico-Chimica Sinica, ;2021, 37(10): 190506. doi: 10.3866/PKU.WHXB201905067 shu

Red Fluorescent Carbon Quantum Dots for Diagnosis of Acidic Microenvironment in Tumors

Jing Huang ¹ ,
Danyang Wang ² ,
Shuhua Li ¹ ,
Hong Fan ^3,, ,
Louzhen Fan ^1,,

1.
College of Chemistry, Beijing Normal University, Beijing 100875, China
2.
Beijing Chaoyang Hospital, Capital Medical University, Beijing 100043, China
3.
Shanxi Provincial People's Hospital, Taiyuan 030012, China

Corresponding author: Hong Fan, fanhong661016@163.com Louzhen Fan, lzfan@bnu.edu.cn
Received Date: 21 May 2019
Revised Date: 9 July 2019
Accepted Date: 11 July 2019
Available Online: 22 July 2019
Fund Project: the National Natural Science Foundation of China 21573019the National Natural Science Foundation of China 21872010

Cancer remains a major global cause of morbidity and mortality. Diagnosis at an early stage can significantly improve the survival of cancer patients. Cancers of different origins often have vastly different genotypes and phenotypes. Therefore, it is challenging to establish a universal strategy for cancer detection. Universal cancer detection can be potentially achieved by using pH-responsive probes. An acidic microenvironment is mainly caused by lactic acid accumulation in rapidly growing tumor cells. Based on the difference in pH between tumor and normal tissues, fluorescent materials that respond to a pH of around 6.8 are ideal for tumor detection. Carbon quantum dots (CQDs) have attracted much attention in bioimaging owing to their outstanding characteristics such as stable photoluminescence, low cytotoxicity, excellent biocompatibility, and resistance to photobleaching. In this study, red fluorescent CQDs (R-CQDs) were synthesized by the solvothermal treatment of 4-(dimethylamino) phenol in the presence of potassium periodate. The UV-Vis spectrum of the R-CQDs showed a characteristic absorption peak at 545 nm. The photoluminescence spectrum revealed an emission peak at 640 nm. The brightness of this photoluminescence peak was quantified to be 12.8% in terms of the absolute quantum yield (QY). Transmission electron microscopy (TEM) images showed that the R-CQDs have uniform sizes with an average diameter of 4 nm and a lattice spacing of 0.21 nm. Fourier transform infrared (FT-IR) spectroscopy and X-ray photoelectron spectroscopy (XPS) confirmed that the R-CQDs have a large number of carboxyl groups. The Raman spectrum of the R-CQDs showed the characteristic D band at 1340 cm^-1 and G band at 1585 cm^-1. The X-ray powder diffraction (XRD) pattern showed a broad (002) peak centered at around 23°. The R-CQDs were responsive to highly acidic or alkaline conditions. The incorporation of a block copolymer (MeO-PEG-PDPA), prepared by atom transfer radical polymerization (ATRP), on the R-CQDs produced pH-responsive fluorescent CQDs (pRF-R-CQDs). Photoluminescence (PL) spectra showed that the pRF-R-CQDs were responsive at pH 6.8. At pH > 6.8, the fluorescence of the pRF-R-CQDs would be quenched because of deprotonation of the amine groups. In contrast, protonation of the amine groups would lead to a dramatic increase in fluorescence emission. TEM images showed that the pRF-R-CQDs self-assemble and disassemble at pH 6.8 because of their pH-responsive properties. Compared with most existing fluorescent materials, the pRF-R-CQDs can effectively resist photobleaching and autofluorescence. Moreover, these pRF-R-CQDs have minimal toxicity and can distinguish tumors from normal tissues. Therefore, pRF-R-CQDs have great potential for use as a universal material in tumor microenvironment diagnosis.
- Red fluorescence,
- Carbon quantum dots,
- pH-response,
- Acidic microenvironment,
- Early diagnosis of Tumor
1. [1]
  Hirsch, F. R.; Franklin, W. A.; Gazdar, A. F.; Bunn, P. A. Clin. Cancer Res. 2001, 7, 5.
2. [2]
  Nothacker, M.; Duda, V.; Hahn, M.; Warm, M.; Degenhardt, F.; Madjar, H.; Weinbrenner, S. Cancer 2009, 9, 335. doi: 10.1186/1471-2407-9-335 doi: 10.1186/1471-2407-9-335
3. [3]
  Nguyen, Q. T.; Tsien, R. Y. Nat. Rev. Cancer 2013, 13, 653. doi: 10.1038/nrc3566 doi: 10.1038/nrc3566
4. [4]
  Shariat, S. F.; Karakiewicz, P. I.; Ashfaq, R.; Lerner, S. P.; Palapattu, G. S.; Cote, R. J.; Sagalowsky, A. I.; Lotan, Y. Cancer 2008, 112, 315. doi: 10.1002/cncr.23162 doi: 10.1002/cncr.23162
5. [5]
  Cheang, M. C. U.; Voduc, D.; Bajdik, C.; Leung, S.; McKinney, S.; Chia, S. K.; Perou, C. M.; Nielsen, T. O. Clin. Cancer Res. 2008, 14, 1368. doi: 10.1158/1078-0432.CCR-07-1658 doi: 10.1158/1078-0432.CCR-07-1658
6. [6]
  Li, T. F.; Li, Y. W.; Xiao, L.; Yu, H. T.; Fan, L. Z. Acta Chim. Sin. 2014, 72, 227. doi: 10.6023/A13101036 doi: 10.6023/A13101036
7. [7]
  Peppercorn, J.; Shapira, I.; Deshields, T.; Kroetz, D.; Friedman, P.; Spears, P.; Collyar, D.; Shulman, L.; Dressler, L.; Bertagnolli, M. Cancer 2012, 118, 5060. doi: 10.1002/cncr.27515 doi: 10.1002/cncr.27515
8. [8]
  Arya, S. K.; Bhansali, S. Chem Rev. 2011, 111, 6783. doi: 10.1021/cr100420s doi: 10.1021/cr100420s
9. [9]
  Stephan, C.; Cammann, H.; Meyer, H. A.; Lein, M.; Jung, K. Cancer Lett. 2007, 249, 18. doi:10.1016/j.canlet.2006.12.031 doi: 10.1016/j.canlet.2006.12.031
10. [10]
  Shukla, H. D.; Mahmood, J.; Vujaskovic, Z. Cancer Lett. 2015, 369, 28. doi: 10.1016/j.canlet.2015.08.003 doi: 10.1016/j.canlet.2015.08.003
11. [11]
  He, P.; Yuan, F. L.; Wang, Z. F.; Tan, Z. A.; Fan, L. Z.; Acta Phys. -Chim. Sin. 2018, 34 (11), 1250. doi: 10.3866/PKU.WHXB201804041
12. [12]
  Vaupel, P.; Kallinowski, F.; Okunieff, P. Cancer Res. 1989, 49, 6449. doi: content/49/23/6449
13. [13]
  Denko, N. C. Nat. Rev. Cancer 2008, 8, 705. doi: 10.1038/nrc2468 doi: 10.1038/nrc2468
14. [14]
  Bissell, M. J.; Hines, W. C. Nat. Med. 2011, 17, 320. doi: 10.1038/nm.2328 doi: 10.1038/nm.2328
15. [15]
  Wang, L.; Li, C. J. Mater. Chem. 2011, 21, 15862. doi: 10.1039/c1jm12072g doi: 10.1039/c1jm12072g
16. [16]
  Webb, B. A.; Chimenti, M.; Jacobson, M. P.; Barber, D. L. Nat. Rev. Cancer 2011, 11, 671. doi: 10.1038/nrc3110 doi: 10.1038/nrc3110
17. [17]
  Vander Heiden, M. G.; Cantley, L. C.; Thompson, C. B. Science 2009, 324, 1029. doi: 10.1126/science.1160809 doi: 10.1126/science.1160809
18. [18]
  Kroemer, G.; Jaattela, M. Nat. Rev. Cancer 2005, 5, 886.
19. [19]
  Tannock, I. F.; Rotin, D. Cancer Res. 1989, 49, 4373.
20. [20]
  Zhang, X.; Lin, Y.; Gillies, R. J. J. Nucl. Med. 2010, 51, 1167. doi: 10.2967/jnumed.109.068981 doi: 10.2967/jnumed.109.068981
21. [21]
  Montet, X.; Ntziachristos, V.; Grimm, J.; Weissleder, R. Cancer Res. 2005, 65, 6330. doi: 10.1158/0008-5472. doi: 10.1158/0008-5472
22. [22]
  Svoronos, A.; Braddock, D. T.; Glazer, P. M.; Engelman, D. M.; Saltzman, W. M.; Slack, F. J. Nature 2015, 518, 107. doi: 10.1038/nature13905 doi: 10.1038/nature13905
23. [23]
  Xie, W. J.; Fu, Y. Y.; Ma, H.; Zhang, M.; Fan, L. Z. Acta Chim. Sin. 2012, 70, 2169. doi: 10.6023/A12060302 doi: 10.6023/A12060302
24. [24]
  Yuan, Y.; Ding, D.; Li, K.; Liu, J.; Liu, B. Small 2014, 10, 1967. doi: 10.1002/smll.201302765 doi: 10.1002/smll.201302765
25. [25]
  Urano, Y.; Asanuma, D.; Hama, Y.; Koyama. Y.; Kamiya, M.; Nagano, T.; Hasegawa, A. Nat. Med. 2009, 15, 104. doi: 10.1038/nm.1854 doi: 10.1038/nm.1854
26. [26]
  Reshetnyak, Y. K.; Andreev, O. A.; Lehnert, U.; Engelman, D. M. Proc. Nat. Acad. Sci. U.S.A. 2006, 103, 6460. doi: 10.1073/pnas.0601463103 doi: 10.1073/pnas.0601463103
27. [27]
  Zhang, M.; Bai, L.; Shang, W.; Xie, W; Fang, D.; Sun, H.; Fan, L.; Han, M.; Liu, C.; Yang, S. J. Mater. Chem. 2012, 22, 7461. doi: 10.1039/c2jm16835a doi: 10.1039/c2jm16835a
28. [28]
  Fan, Z.; Li, Y.; Li, X.; Fan, L.; Zhou, S.; Fang, D.; Yang, S. Carbon 2014, 70, 149-156. doi: 10.1016/j.carbon.2013.12.085 doi: 10.1016/j.carbon.2013.12.085
29. [29]
  Yuan, F.; Wang, Z.; Li, S.; Tan, Z.; Fan, L.; Yang, S. Adv. Mater. 2017, 29, 1604436. doi: 10.1002/adma.201604436 doi: 10.1002/adma.201604436
30. [30]
  Yuan, F.; Yuan, T.; Sui, L.; Wang, Z.; Fan, L.; Tan, Z. Nat. Commun. 2018, 9, 2249. doi: 10.1038/s41467-018-04635-5 doi: 10.1038/s41467-018-04635-5
31. [31]
  Gong, N.; Ma, X.; Ye, X.; Zhou, Q.; Chen, X.; Tan, X.; Yao, S.; Huo, S; Zhang, T.; Chen, S.; et al. Nat. Nanotech. 2019, 14, 379. doi: 10.1038/s41565-019-0373-6 doi: 10.1038/s41565-019-0373-6
32. [32]
  Chen, D.; Feng, H. B.; Li, J. Chem. Rev. 2012, 112, 6027. doi: 10.1021/cr300115g doi: 10.1021/cr300115g
33. [33]
  Xi, Z. F.; Yuan, F. L.; Wang, Z. F; Li, S. H.; Fan, L. Z. Acta Chim. Sin. 2018, 76, 460. doi: 10.6023/A18020048 doi: 10.6023/A18020048
34. [34]
  Fan, Z.; Zhou, S.; Garcia, C.; Fan, L.; Zhou, J. Nanoscale 2017, 9, 4928. doi: 10.1039/c7nr00888k doi: 10.1039/c7nr00888k
35. [35]
  Li, S.; Zhou, S.; Li, Y.; Zhu, J.; Fan, L.; Yang, S. ACS Appl. Mater. Interfaces 2017, 9, 22332. doi: 10.1021/acsami.7b07267 doi: 10.1021/acsami.7b07267
36. [36]
  Sun, M.; Liu, H.; Liu, Y.; Qu, J.; Li, J. Nanoscale, 2015, 7, 1250. doi: 10.1039/c4nr05838k doi: 10.1039/c4nr05838k
37. [37]
  Helmlinger, G.; Yuan, F.; Dellian, M.; Jain, R. K. Nat. Med. 1997, 3, 177. doi: 10.1038/nm0297-177 doi: 10.1038/nm0297-177
38. [38]
  Volk, T.; Jahde, E.; Fortmeyer, H. P.; Glusenkamp, K. H.; Rajewsky, M. F. Br. J. Cancer 1993, 68, 492. doi: 10.1038/bjc.1993.375 doi: 10.1038/bjc.1993.375
39. [39]
  Wang, Y.; Zhou, K.; Huang, G.; Hensley, C.; Huang, X.; Ma, X.; Zhao, T.; Sumer, B. D.; DeBerardinis, R. J.; Gao, J. Nat. Mater. 2014, 13, 204. doi: 10.1038/NMAT3819 doi: 10.1038/NMAT3819
40. [40]
  Li, C.; Xia, J. A.; Wei, X. B.; Yan, H. H.; Si, Z.; Ju, S. H. Adv. Funct. Mater. 2010, 20, 2222. doi: 10.1002/adfm.201000038 doi: 10.1002/adfm.201000038
41. [41]
  Li, L.; Ji, J.; Fei, R.; Wang, C.; Lu, Q.; Zhang, J.; Jiang, L.; Zhu, J. Adv. Funct. Mater. 2012, 22, 2971. doi: 10.1002/adfm.201200166 doi: 10.1002/adfm.201200166
42. [42]
  Zheng, X.; Than, A.; Ananthanaraya, A.; Kim, D.; Chen, P. ACS Nano 2013, 7, 6278. doi: 10.1021/nn4023137 doi: 10.1021/nn4023137
43. [43]
  Zhou, K. J.; Liu, H. M.; Zhang, S.R.; Huang, X. N.; Wang, Y. G.; Huang G.; Sumer, B. D.; Gao, J. M. J. Am. Chem. Soc. 2012, 134, 7803. doi: 10.1021/ja300176w doi: 10.1021/ja300176w
44. [44]
  Hu, C.; Mu, Y.; Li, M.; Qiu, J. Acta Phys. -Chim. Sin. 2019, 35 (6), 572. doi: 10.3866/PKU.WHXB201806060
45. [45]
  Zhu, S.; Zhang, J; Qiao, C.; Tang, S.; Li, Y.; Yuan, W.; Li, B.; Tian, L.; Liu, F.; Hu, R.; et al. Chem. Commun. 2011, 47, 6858. doi: 10.1039/C1CC11122A doi: 10.1039/C1CC11122A
46. [46]
  Jain, R. K. Cancer Metast. Rev. 1987, 6, 559. doi: 10.1007/BF00047468 doi: 10.1007/BF00047468
1. [1]
  Shijie Li , Ke Rong , Xiaoqin Wang , Chuqi Shen , Fang Yang , Qinghong Zhang . Design of Carbon Quantum Dots/CdS/Ta₃N₅ S-Scheme Heterojunction Nanofibers for Efficient Photocatalytic Antibiotic Removal. Acta Physico-Chimica Sinica, 2024, 40(12): 2403005-. doi: 10.3866/PKU.WHXB202403005
2. [2]
  Chengcheng Si , Linshan Chai , Huiyuan Liu , Liye Sun , Shijian Cheng , Hailing Li , Wenyun Wang , Fang Liu , Qing Feng , Min Liu . Harry Potter China Tour Themed Innovative Science Popularization Experiment: Chemistry Magic Meets the Real World at Wuhan Station. University Chemistry, 2024, 39(9): 283-287. doi: 10.12461/PKU.DXHX202401069
3. [3]
  Jianjun Liu , Xue Yang , Chi Zhang , Xueyu Zhao , Zhiwei Zhang , Yongmei Chen , Qinghong Xu , Shao Jin . Preparation and Fluorescence Characterization of CdTe Semiconductor Quantum Dots. University Chemistry, 2024, 39(7): 307-315. doi: 10.3866/PKU.DXHX202311031
4. [4]
  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
5. [5]
  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
6. [6]
  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
7. [7]
  Miaomiao He , Zhiqing Ge , Qiang Zhou , Jiaqing He , Hong Gong , Lingling Li , Pingping Zhu , Wei Shao . Exploring the Fascinating Realm of Quantum Dots. University Chemistry, 2024, 39(6): 231-237. doi: 10.3866/PKU.DXHX202310040
8. [8]
  Zeyu XU , Anlei DANG , Bihua DENG , Xiaoxin ZUO , Yu LU , Ping YANG , Wenzhu YIN . Evaluation of the efficacy of graphene oxide quantum dots as an ovalbumin delivery platform and adjuvant for immune enhancement. Chinese Journal of Inorganic Chemistry, 2024, 40(6): 1065-1078. doi: 10.11862/CJIC.20240099
9. [9]
  Yueguang Chen , Wenqiang Sun . “Carbon” Adventures. University Chemistry, 2024, 39(9): 248-253. doi: 10.3866/PKU.DXHX202308074
10. [10]
  Yuping Wei , Yiting Wang , Jialiang Jiang , Jinxuan Deng , Hong Zhang , Xiaofei Ma , Junjie Li . Interdisciplinary Teaching Practice——Flexible Wearable Electronic Skin for Low-Temperature Environments. University Chemistry, 2024, 39(10): 261-270. doi: 10.12461/PKU.DXHX202404007
11. [11]
  Xiyuan Su , Zhenlin Hu , Ye Fan , Xianyuan Liu , Xianyong Lu . Change as You Want: Multi-Responsive Superhydrophobic Intelligent Actuation Material. University Chemistry, 2024, 39(5): 228-237. doi: 10.3866/PKU.DXHX202311059
12. [12]
  Nana Wang , Gaosheng Zhang , Huosheng Li , Tangfu Xiao . Discussion on the Teaching Reform of Environmental Functional Materials within the Context of “Double First-Class” Initiative: Emphasizing the Integration of Industry, Academia, Research, and Application. University Chemistry, 2024, 39(6): 137-144. doi: 10.3866/PKU.DXHX202312010
13. [13]
  Baohua LÜ , Yuzhen LI . Anisotropic photoresponse of two-dimensional layered α-In₂Se₃(2H) ferroelectric materials. Chinese Journal of Inorganic Chemistry, 2024, 40(10): 1911-1918. doi: 10.11862/CJIC.20240105
14. [14]
  Jianye Kang , Xinyu Yang , Xuhao Yang , Jiahui Sun , Yuhang Liu , Shutao Wang , Wenlong Song . Carbon dots-enhanced pH-responsive lubricating hydrogel based on reversible dynamic covalent bondings. Chinese Chemical Letters, 2024, 35(5): 109297-. doi: 10.1016/j.cclet.2023.109297
15. [15]
  Shuang Li , Jiayu Sun , Guocheng Liu , Shuo Zhang , Zhong Zhang , Xiuli Wang . A new Keggin-type polyoxometallate-based bifunctional catalyst for trace detection and pH-universal photodegradation of phenol. Chinese Chemical Letters, 2024, 35(8): 109148-. doi: 10.1016/j.cclet.2023.109148
16. [16]
  Rui Wang , He Qi , Haijiao Zheng , Qiong Jia . Light/pH dual-responsive magnetic metal-organic frameworks composites for phosphorylated peptide enrichment. Chinese Chemical Letters, 2024, 35(7): 109215-. doi: 10.1016/j.cclet.2023.109215
17. [17]
  Yan Liu , Yang Wang , Jiayi Zhu , Xuxian Su , Xudong Lin , Liang Xu , Xiwen Xing . Employing pH-responsive RNA triplex to control CRISPR/Cas9-mediated gene manipulation in mammalian cells. Chinese Chemical Letters, 2024, 35(9): 109427-. doi: 10.1016/j.cclet.2023.109427
18. [18]
  Tongyu Zheng , Teng Li , Xiaoyu Han , Yupei Chai , Kexin Zhao , Quan Liu , Xiaohui Ji . A DIY pH Detection Agent Using Persimmon Extract for Acid-Base Discoloration Popularization Experiment. University Chemistry, 2024, 39(5): 27-36. doi: 10.3866/PKU.DXHX202309107
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]
  Lei Shu , Zimin Duan , Yushen Kang , Zijian Zhao , Hong Wang , Lihua Zhu , Hui Xiong , Nan Wang . An Exploration of the CO₂-Involved Carbon Cycle World. University Chemistry, 2024, 39(5): 144-153. doi: 10.3866/PKU.DXHX202309084

Get Citation

PDF

XML

Metrics

PDF Downloads(12)
Abstract views(609)
HTML views(174)

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