细胞膜锚定的纳米工程化碳点作为焦亡放大器用于增强的肿瘤光动力免疫治疗

引用本文: 陈铁金, 薛小矿, 李建, 崔敏辉, 郝永梁, 薛面起, 肖海华, 葛介超, 汪鹏飞. 细胞膜锚定的纳米工程化碳点作为焦亡放大器用于增强的肿瘤光动力免疫治疗[J]. 物理化学学报, 2025, 41(10): 100113. doi: 10.1016/j.actphy.2025.100113 shu

Citation: Tiejin Chen, Xiaokuang Xue, Jian Li, Minhui Cui, Yongliang Hao, Mianqi Xue, Haihua Xiao, Jiechao Ge, Pengfei Wang. Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy[J]. Acta Physico-Chimica Sinica, 2025, 41(10): 100113. doi: 10.1016/j.actphy.2025.100113 shu

细胞膜锚定的纳米工程化碳点作为焦亡放大器用于增强的肿瘤光动力免疫治疗

陈铁金 ^{1, 3,} ,
薛小矿 ^{1, 3,} ,
李建 ^{1, 3,} ,
崔敏辉 ^2, ,
郝永梁 ^{1, 3,} ,
薛面起 ^1, ,
肖海华 ^{2,
,} ,
葛介超 ^{1, 3,
,} ,
汪鹏飞 ^{1, 3,}

1.
中国科学院理化技术研究所, 北京 100190
2.
中国科学院化学研究所, 北京 100190
3.
中国科学院大学未来技术学院, 北京 100049

通讯作者: 肖海华, hhxiao@iccas.ac.cn; 葛介超, jchge2010@mail.ipc.ac.cn

基金项目:
国家自然科学基金 52272052

国家重点研发计划 2022YFA1207600

摘要: 光动力疗法(PDT)作为一种美国食品药品监督管理局(FDA)批准的治疗手段，在肿瘤治疗领域取得了显著进展。然而，传统的PDT由于活性氧(ROS)的瞬时性、过度的光毒性以及诱导经典凋亡的特性，可能导致预后效果较差。本研究利用带正电荷的碳点光敏剂(PCDs)与新吲哚菁绿(IR820)之间的静电相互作用构建了一种纳米工程化碳点(NCDs)。通过调控IR820的引入比例，可改变NCDs的表面电荷与两亲性特征，从而优化其细胞膜锚定能力。此外，IR820的J聚集导致其荧光从NIR-Ⅰ区红移到NIR-Ⅱ区，从而实现NIR-Ⅱ成像。值得注意的是，IR820对PCDs的光活性具有淬灭作用，因此，NCDs的PDT效应依赖于750 nm激光照射下IR820的光漂白和577 nm激光照射下PCDs的光动力。最终，体外与体内实验均表明，在级联激光照射下，膜靶向的NCDs可以有效增强肿瘤细胞焦亡，从而以最小副作用实现肿瘤清除，同时激活免疫响应以抑制肿瘤的肺转移。本研究开发了一种多功能的纳米工程化碳点，提供了一种可控性强、治疗效果好以及安全性高的肿瘤光动力免疫治疗新策略，展现出良好的临床应用前景。

关键词:

English

Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy

1.
Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China
2.
Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China
3.
School of Future Technology, University of Chinese Academy of Sciences, Beijing 100049, China

Corresponding author: Email: hhxiao@iccas.ac.cn (H. Xiao); Email: jchge2010@mail.ipc.ac.cn (J. Ge)

Received Date: 29 April 2025
Accepted Date: 08 June 2025
Revised Date: 05 June 2025
Available Online: 15 October 2025
Fund Project:
the National Natural Science Foundation of China

the National Key Research and Development Program of China

Abstract: Photodynamic therapy (PDT), as a Food and Drug Administration (FDA)-approved therapeutic modality, has witnessed substantial advancements in the field of oncology. However, the conventional PDT may suffer poor prognosis due to the transient nature of (Reactive Oxygen Species) ROS, excessive phototoxicity, and inducing traditional apoptosis. In this study, a nanoengineered carbon dots (NCDs) was constructed through electrostatic interaction between a positive-charged carbon dots photosensitizers (PCDs) and new indocyanine green (IR820). The introduction of IR820 at variable ratios could change the surface charge and amphiphilic characteristics of NCDs, thereby modulating the membrane-anchoring capability of NCDs. Besides, the J-aggregation of IR820 led to a redshift of fluorescence from NIR-Ⅰ to NIR-Ⅱ region, thereby achieving NIR-Ⅱ imaging. Furthermore, the photoactivity of PCDs was quenched by IR820, with subsequent restoration of PDT occurring contingent on the photobleaching of IR820 via 750 nm laser irradiation. Finally, both in vitro and in vivo studies had demonstrated that under a cascaded laser irradiation, the membrane-targeted NCDs could effectively induce cell pyroptosis, thereby eradicating tumors with minimal side effects while simultaneously activating immune responses to inhibit tumor lung metastasis. This study developed a multifunctional nanoengieering carbon dots and offered novel perspectives for tumor photodynamic-immunotherapy with enhanced controllability, improved efficacy and high security.

Key words:

1. [1]
  Y. Wang, K. Ma, M. Kang, D. Yan, N. Niu, S. Yan, P. Sun, L. Zhang, L. Sun, D. Wang, et al., Chem. Soc. Rev. 53 (2024) 12014, https://doi.org/10.1039/D4CS00708E. doi: 10.1039/D4CS00708E
2. [2]
  E. Nestoros, A. Sharma, E. Kim, J. S. Kim, M. Vendrell, Nat. Rev. Chem. 9 (2025) 46, https://doi.org/10.1038/s41570-024-00662-7. doi: 10.1038/s41570-024-00662-7
3. [3]
  T. C. Pham, V. N. Nguyen, Y. Choi, S. Lee, J. Yoon, Chem. Rev. 121 (2021) 13454, https://doi.org/10.1021/acs.chemrev.1c00381. doi: 10.1021/acs.chemrev.1c00381
4. [4]
  J. Kang, H. Jeong, M. Jeong, J. Kim, S. Park, J. Jung, J. M. An, D. Kim, J. Am. Chem. Soc. 145 (2023) 27587, https://doi.org/10.1021/jacs.3c09339. doi: 10.1021/jacs.3c09339
5. [5]
  L. Li, X. Zhang, Y. Ren, Q. Yuan, Y. Wang, B. Bao, M. Li, Y. Tang, J. Am. Chem. Soc. 146 (2024) 5927, https://doi.org/10.1021/jacs.3c12132. doi: 10.1021/jacs.3c12132
6. [6]
  X. Qu, F. Yin, M. Pei, Q. Chen, Y. Zhang, S. Lu, X. Zhang, Z. Liu, X. Li, H. Chen, et al., ACS Nano 17 (2023) 11466, https://doi.org/10.1021/acsnano.3c01308. doi: 10.1021/acsnano.3c01308
7. [7]
  L. Feng, D. Tao, Z. Dong, Q. Chen, Y. Chao, Z. Liu, M. Chen, Biomaterials 127 (2017) 13, https://doi.org/10.1016/j.biomaterials.2016.11.027. doi: 10.1016/j.biomaterials.2016.11.027
8. [8]
  X. Zhang, J. Xiong, K. Wang, H. Yu, B. Sun, H. Ye, Z. Zhao, N. Wang, Y. Wang, S. Zhang, et al., Bioact. Mater. 6 (2021) 2291, https://doi.org/10.1016/j.bioactmat.2021.01.004. doi: 10.1016/j.bioactmat.2021.01.004
9. [9]
  M. Dirak, C. M. Yenici, S. Kolemen, Coord. Chem. Rev. 506 (2024) 215710, https://doi.org/10.1016/j.ccr.2024.215710. doi: 10.1016/j.ccr.2024.215710
10. [10]
  J. B. Zhuang, Z. D. Ma, N. Li, H. Chen, L. J. Yang, Y. Lu, K. Y. Guo, N. Zhao, B. Z. Tang, Adv. Mater. 36 (2024) 2309488, https://doi.org/10.1002/adma.202309488. doi: 10.1002/adma.202309488
11. [11]
  F. H. Igney, P. H. Krammer, Nat. Rev. Cancer 2 (2002) 277, https://doi.org/10.1038/nrc776. doi: 10.1038/nrc776
12. [12]
  K. Hadian, B. R. Stockwell, Nat. Rev. Drug Discov. 22 (2023) 723, https://doi.org/10.1038/s41573-023-00749-8. doi: 10.1038/s41573-023-00749-8
13. [13]
  X. Sun, M. Li, P. Wang, Q. Bai, X. Cao, D. Mao, Small Methods 7 (2023) 2201614, https://doi.org/10.1002/smtd.202201614. doi: 10.1002/smtd.202201614
14. [14]
  W. T. Gao, X. Y. Wang, Y. Zhou, X. Q. Wang, Y. Yu, Sig. Transdut. Target. Ther. 7 (2022) 196, https://doi.org/10.1038/s41392-022-01046-3. doi: 10.1038/s41392-022-01046-3
15. [15]
  P. Fontana, G. Du, Y. Zhang, H. Zhang, S. M. Vora, J. J. Hu, M. Shi, A. B. Tufan, L. B. Healy, S. Xia, et al., Cell 187 (2024) 6165, https://doi.org/10.1016/j.cell.2024.08.007. doi: 10.1016/j.cell.2024.08.007
16. [16]
  Q. Y. Wang, Y. P. Wang, J. J. Ding, C. H. Wang, X. H. Zhou, W. Q. Gao, H. W. Huang, F. Shao, Z. B. Liu, Nature 579 (2020) 421, https://doi.org/10.1038/s41586-020-2079-1. doi: 10.1038/s41586-020-2079-1
17. [17]
  Z. B. Zhang, Y. Zhang, S. Y. Xia, Q. Kong, S. Y. Li, X. Liu, C. Junqueira, K. F. Meza-Sosa, T. M. Y. Mok, J. Ansara, et al., Nature 579 (2020) 415, https://doi.org/10.1038/s41586-020-2071-9. doi: 10.1038/s41586-020-2071-9
18. [18]
  Z. He, D. Feng, C. Zhang, Z. Chen, H. Wang, J. Hou, S. Li, X. Wei, J. Control. Release 366 (2024) 375, https://doi.org/10.1016/j.jconrel.2023.12.023. doi: 10.1016/j.jconrel.2023.12.023
19. [19]
  M. Wu, X. G. Liu, H. Chen, Y. K. Duan, J. J. Liu, Y. T. Pan, B. Liu, Angew. Chem. Int. Ed. 60 (2021) 9093, https://doi.org/10.1002/anie.202016399. doi: 10.1002/anie.202016399
20. [20]
  M. Li, J. Kim, H. Rha, S. Son, M. S. Levine, Y. Xu, J. L. Sessler, J. S. Kim, J. Am. Chem. Soc. 145 (2023) 6007, https://doi.org/10.1021/jacs.3c01231. doi: 10.1021/jacs.3c01231
21. [21]
  M. Wang, M. Wu, X. Liu, S. Shao, J. Huang, B. Liu, T. Liang, Adv. Sci. 9 (2022) 2202914, https://doi.org/10.1002/advs.202202914. doi: 10.1002/advs.202202914
22. [22]
  Z. G. Yi, X. J. Qin, L. Zhang, H. Chen, T. L. Song, Z. C. Luo, T. Wang, J. Lau, Y. L. Wu, T. B. Toh, et al., J. Am. Chem. Soc. 146 (2024) 9413, https://doi.org/10.1021/jacs.4c01929. doi: 10.1021/jacs.4c01929
23. [23]
  Q. Liu, X. Yao, L. Zhou, W. Wu, J. Cheng, Z. Zhang, Z. Li, H. Sun, J. Jin, M. Zhang, et al., Adv. Mater. 36 (2024) 2401145, https://doi.org/10.1002/adma.202401145. doi: 10.1002/adma.202401145
24. [24]
  X. Wu, J. J. Hu, J. Yoon, Angew. Chem. Int. Ed. 63 (2024) e202400249, https://doi.org/10.1002/anie.202400249. doi: 10.1002/anie.202400249
25. [25]
  C. Xiang, Y. Liu, Q. Ding, T. Jiang, C. Li, J. Xiang, X. Yang, T. Yang, Y. Wang, Y. Tan, et al., Adv. Funct. Mater. 35 (2024) 2417979, https://doi.org/10.1002/adfm.202417979. doi: 10.1002/adfm.202417979
26. [26]
  Z. Li, F. Mo, Y. Wang, W. Li, Y. Chen, J. Liu, T. -J. Chen-Mayfield, Q. Hu, Nat. Commun. 13 (2022) 6321, https://doi.org/10.1038/s41467-022-34036-8. doi: 10.1038/s41467-022-34036-8
27. [27]
  Y. Q. Tang, H. K. Bisoyi, X. M. Chen, Z. Y. Liu, X. Chen, S. Zhang, Q. Li, Adv. Mater. 35 (2023) 2300232, https://doi.org/10.1002/adma.202300232. doi: 10.1002/adma.202300232
28. [28]
  Y. Liu, Z. Huang, X. Wang, Y. Hao, J. Yang, H. Wang, S. Qu, Adv. Funct. Mater. 35 (2025) 2420587, https://doi.org/10.1002/adfm.202420587. doi: 10.1002/adfm.202420587
29. [29]
  B. Y. Wang, S. Y. Lu, Matter 5 (2022) 110, https://doi.org/10.1016/j.matt.2021.10.016. doi: 10.1016/j.matt.2021.10.016
30. [30]
  L. Jiang, H. Cai, W. W. Zhou, Z. J. Li, L. Zhang, H. Bi, Adv. Mater. 35 (2023) 2210776, https://doi.org/10.1002/adma.202210776. doi: 10.1002/adma.202210776
31. [31]
  J. C. Ge, M. H. Lan, B. J. Zhou, W. M. Liu, L. Guo, H. Wang, Q. Y. Jia, G. L. Niu, X. Huang, H. Y. Zhou, et al., Nat. Commun. 5 (2014) 4596, https://doi.org/10.1038/ncomms5596. doi: 10.1038/ncomms5596
32. [32]
  S. H. Li, W. Su, H. Wu, T. Yuan, C. Yuan, J. Liu, G. Deng, X. C. Gao, Z. M. Chen, Y. M. Bao, et al. , Nat. Biomed. Eng. 4 (2020) 704, https://doi.org/10.1038/s41551-020-0540-y. doi: 10.1038/s41551-020-0540-y
33. [33]
  L. Ðorđević, F. Arcudi, M. Cacioppo, M. Prato, Nat. Nanotechnol. 17 (2022) 112, https://doi.org/10.1038/s41565-021-01051-7. doi: 10.1038/s41565-021-01051-7
34. [34]
  T. Han, Y. Wang, S. Ma, M. Li, N. Zhu, S. Tao, J. Xu, B. Sun, Y. Jia, Y. Zhang, et al., Adv. Sci. 9 (2022) 2203474, https://doi.org/10.1002/advs.202203474. doi: 10.1002/advs.202203474
35. [35]
  H. Sun, S. Sun, H. Wang, K. Cheng, Y. Zhou, X. Wang, S. Gao, J. Mo, S. Li, H. Lin, et al., Acta Biomater. 194 (2025) 352, https://doi.org/10.1016/j.actbio.2025.01.030. doi: 10.1016/j.actbio.2025.01.030
36. [36]
  Y. Zhang, Q. Jia, F. Nan, J. Wang, K. Liang, J. Li, X. Xue, H. Ren, W. Liu, J. Ge, et al., Biomaterials 293 (2023) 121953, https://doi.org/10.1016/j.biomaterials.2022.121953. doi: 10.1016/j.biomaterials.2022.121953
37. [37]
  X. Zhang, L. Li, B. Wang, Z. Cai, B. Zhang, F. Chen, G. Xing, K. Li, S. Qu, Angew. Chem. Int. Ed. 63 (2024) e202410522, https://doi.org/10.1002/anie.202410522. doi: 10.1002/anie.202410522
38. [38]
  B. Wang, G. I. N. Waterhouse, B. Yang, S. Lu, Acc. Chem. Res. 57 (2024) 2928, https://doi.org/10.1021/acs.accounts.4c00516. doi: 10.1021/acs.accounts.4c00516
39. [39]
  Q. Cheng, T. Zhang, Q. Wang, X. Wu, L. Li, R. Lin, Y. Zhou, S. Qu, Adv. Mater. 36 (2024) 2408685, https://doi.org/10.1002/adma.202408685. doi: 10.1002/adma.202408685
40. [40]
  T. Chen, K. Liang, J. Wang, J. Li, X. Xue, Y. Hao, H. Liang, H. Ren, H. Xiao, J. Ge, et al., Nano Lett. 24 (2024) 14709, https://doi.org/10.1021/acs.nanolett.4c03913. doi: 10.1021/acs.nanolett.4c03913
41. [41]
  J. Yang, B. Ren, X. Yin, L. Xiang, Y. Hua, X. Huang, H. Wang, Z. Mao, W. Chen, J. Deng, Adv. Mater. 36 (2024) 2402720, https://doi.org/10.1002/adma.202402720. doi: 10.1002/adma.202402720
42. [42]
  Y. J. Li, Y. C. Guo, K. X. Zhang, R. R. Zhu, X. Y. Chen, Z. Z. Zhang, W. J. Yang, Adv. Sci. 11 (2024) 2306580, https://doi.org/10.1002/advs.202306580. doi: 10.1002/advs.202306580
43. [43]
  J. Xu, X. Zheng, T. -B. Ren, L. Shi, X. Yin, L. Yuan, X. -B. Zhang, Coord. Chem. Rev. 528 (2025) 216379, https://doi.org/10.1016/j.ccr.2024.216379. doi: 10.1016/j.ccr.2024.216379
44. [44]
  Y. Li, D. Hu, M. Pan, Y. Qu, B. Chu, J. Liao, X. Zhou, Q. Liu, S. Cheng, Y. Chen, et al., Biomaterials 288 (2022) 121700, https://doi.org/10.1016/j.biomaterials.2022.121700. doi: 10.1016/j.biomaterials.2022.121700
45. [45]
  D. -T. Nguyen, M. -J. Baek, S. M. Lee, D. Kim, S. -Y. Yoo, J. -Y. Lee, D. -D. Kim, Nat. Nanotechnol. 19 (2024) 1723, https://doi.org/10.1038/s41565-024-01757-4. doi: 10.1038/s41565-024-01757-4
46. [46]
  M. Yu, S. Li, X. Ren, N. Liu, W. Guo, J. Xue, L. Tan, C. Fu, Q. Wu, M. Niu, et al., ACS Nano 18 (2024) 3636, https://doi.org/10.1021/acsnano.3c11433. doi: 10.1021/acsnano.3c11433
47. [47]
  H. Xia, W. Zhou, D. Li, F. Peng, L. Yu, Y. Sang, H. Liu, A. Hao, J. Qiu, Angew. Chem. Int. Ed. 63 (2024) e202312755, https://doi.org/10.1002/anie.202312755. doi: 10.1002/anie.202312755
48. [48]
  T. Zhang, X. Yang, X. Ou, M. M. S. Lee, J. Zhang, C. Xu, X. Yu, P. Gong, J. W. Y. Lam, P. Zhang, et al., Adv. Mater. 35 (2023) 2303186, https://doi.org/10.1002/adma.202303186. doi: 10.1002/adma.202303186
49. [49]
  L. H. Liu, W. X. Qiu, Y. H. Zhang, B. Li, C. Zhang, F. Gao, L. Zhang, X. Z. Zhang, Adv. Funct. Mater. 27 (2017) 1700220, https://doi.org/10.1002/adfm.201700220. doi: 10.1002/adfm.201700220
50. [50]
  S. J. Hao, Y. X. Zhu, F. G. Wu, J. Control. Release. 357 (2023) 222, https://doi.org/10.1016/j.jconrel.2023.03.038. doi: 10.1016/j.jconrel.2023.03.038
51. [51]
  K. Minton, Nat. Rev. Mmunol. 20 (2020) 274, https://doi.org/10.1038/s41577-020-0297-2. doi: 10.1038/s41577-020-0297-2

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

细胞膜锚定的纳米工程化碳点作为焦亡放大器用于增强的肿瘤光动力免疫治疗

通讯作者: 肖海华, hhxiao@iccas.ac.cn; 葛介超, jchge2010@mail.ipc.ac.cn

English

Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy

Corresponding author: Email: hhxiao@iccas.ac.cn (H. Xiao); Email: jchge2010@mail.ipc.ac.cn (J. Ge)

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中国化学会秘书处

细胞膜锚定的纳米工程化碳点作为焦亡放大器用于增强的肿瘤光动力免疫治疗

通讯作者: 肖海华, hhxiao@iccas.ac.cn; 葛介超, jchge2010@mail.ipc.ac.cn

English

Membrane-anchoring nanoengineered carbon dots as a pyroptosis amplifier for robust tumor photodynamic-immunotherapy

Corresponding author: Email: hhxiao@iccas.ac.cn (H. Xiao); Email: jchge2010@mail.ipc.ac.cn (J. Ge)

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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