红色荧光碳量子点用于肿瘤微酸环境诊断

引用本文: 黄靖, 王丹阳, 李淑花, 范红, 范楼珍. 红色荧光碳量子点用于肿瘤微酸环境诊断[J]. 物理化学学报, 2021, 37(10): 190506. doi: 10.3866/PKU.WHXB201905067 shu

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

红色荧光碳量子点用于肿瘤微酸环境诊断

黄靖 ^1, ,
王丹阳 ^2, ,
李淑花 ^1, ,
范红 ^{3,
,} ,
范楼珍 ^{1,
,}

1.
北京师范大学化学学院，北京 100875
2.
首都医科大学附属北京朝阳医院，北京 100043
3.
山西省人民医院，太原 030012

通讯作者: 范红, fanhong661016@163.com; 范楼珍, lzfan@bnu.edu.cn

基金项目:
国家自然科学基金 21573019

国家自然科学基金 21872010

摘要: 实现肿瘤的早期诊断对于提高癌症患者的存活率或延长生存时间非常重要。由于肿瘤细胞的糖酵解失调，导致肿瘤组织呈现微酸环境(pH < 6.8)，因此可以通过设计在pH 6.8响应的荧光材料实现对于肿瘤的早期诊断。在本工作中，我们以4-二甲氨基苯酚为前驱体，高碘酸钾为氧化剂，采用溶剂热法制备了发射波长为640 nm的水溶性红色荧光碳量子点(R-CQDs)。将单甲醚聚乙二醇衍生物(MeO-PEG-PDPA)修饰到R-CQDs表面，获得在pH 6.8响应的R-CQDs (pRF-R-CQDs)，pH < 6.8时呈现红色荧光，pH > 6.8时荧光淬灭。通过透射电子显微镜(TEM)、X射线光电子能谱(XPS)、傅里叶变换红外(FT-IR)光谱、拉曼(Raman)光谱、X射线粉末衍射(XRD)图谱、荧光(PL)光谱、紫外可见(UV-Vis)吸收光谱对R–CQDs进行结构与性质测定。研究了pRF-R-CQDs在组织成像及活体成像中的应用。结果表明：肿瘤微酸环境(pH < 6.8)中，pRF-R-CQDs的氨基质子化而呈现红色荧光。正常组织(pH > 6.8)中，pRF-R-CQDs的氨基去质子化导致荧光淬灭。pRF-R-CQDs的浓度在高达100 μg·mL^-1时仍未表现出明显的细胞毒性。pRF-R-CQDs能够用于区分出肿瘤和正常组织，可用于肿瘤的早期诊断。

关键词:

English

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: Email: fanhong661016@163.com (H.F); Email: lzfan@bnu.edu.cn (L.F.), Tel.: +86-10-58805372

Received Date: 21 May 2019
Accepted Date: 11 July 2019
Revised Date: 09 July 2019
Available Online: 15 October 2021
Fund Project:
the National Natural Science Foundation of China

the National Natural Science Foundation of China

Abstract: 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.

Key words:

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
3. [3]
  Nguyen, Q. T.; Tsien, R. Y. Nat. Rev. Cancer 2013, 13, 653. 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
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
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
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
8. [8]
  Arya, S. K.; Bhansali, S. Chem Rev. 2011, 111, 6783. 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
10. [10]
  Shukla, H. D.; Mahmood, J.; Vujaskovic, Z. Cancer Lett. 2015, 369, 28. doi: 10.1016/j.canlet.2015.08.003
11. [11]
  贺平, 袁方龙, 王子飞, 谭占鳌, 范楼珍.物理化学学报, 2018, 34 (11), 1250.doi: 10.3866/PKU.WHXB201804041He, 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
14. [14]
  Bissell, M. J.; Hines, W. C. Nat. Med. 2011, 17, 320. doi: 10.1038/nm.2328
15. [15]
  Wang, L.; Li, C. J. Mater. Chem. 2011, 21, 15862. 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
17. [17]
  Vander Heiden, M. G.; Cantley, L. C.; Thompson, C. B. Science 2009, 324, 1029. 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
21. [21]
  Montet, X.; Ntziachristos, V.; Grimm, J.; Weissleder, R. Cancer Res. 2005, 65, 6330. 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
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
24. [24]
  Yuan, Y.; Ding, D.; Li, K.; Liu, J.; Liu, B. Small 2014, 10, 1967. 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
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
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
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
29. [29]
  Yuan, F.; Wang, Z.; Li, S.; Tan, Z.; Fan, L.; Yang, S. Adv. Mater. 2017, 29, 1604436. 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
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
32. [32]
  Chen, D.; Feng, H. B.; Li, J. Chem. Rev. 2012, 112, 6027. 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
34. [34]
  Fan, Z.; Zhou, S.; Garcia, C.; Fan, L.; Zhou, J. Nanoscale 2017, 9, 4928. 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
36. [36]
  Sun, M.; Liu, H.; Liu, Y.; Qu, J.; Li, J. Nanoscale, 2015, 7, 1250. 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
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
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
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
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
42. [42]
  Zheng, X.; Than, A.; Ananthanaraya, A.; Kim, D.; Chen, P. ACS Nano 2013, 7, 6278. 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
44. [44]
  胡超, 穆野, 李明宇, 邱介山.物理化学学报, 2019, 35 (6), 572. doi: 10.3866/PKU.WHXB201806060Hu, 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
46. [46]
  Jain, R. K. Cancer Metast. Rev. 1987, 6, 559. doi: 10.1007/BF00047468

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

红色荧光碳量子点用于肿瘤微酸环境诊断

通讯作者: 范红, fanhong661016@163.com; 范楼珍, lzfan@bnu.edu.cn

English

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

Corresponding author: Email: fanhong661016@163.com (H.F); Email: lzfan@bnu.edu.cn (L.F.), Tel.: +86-10-58805372

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

红色荧光碳量子点用于肿瘤微酸环境诊断

通讯作者: 范红, fanhong661016@163.com; 范楼珍, lzfan@bnu.edu.cn

English

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

Corresponding author: Email: fanhong661016@163.com (H.F); Email: lzfan@bnu.edu.cn (L.F.), Tel.: +86-10-58805372

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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