Citation: Lizhuang Zhong, Ming Liu, Shilong Su, Dongxin Zeng, Jing Hu, Zhiqian Guo. Engineering stimuli-responsive block copolymers for multimodal bioimaging[J]. Chinese Chemical Letters, ;2026, 37(1): 111512. doi: 10.1016/j.cclet.2025.111512 shu

Engineering stimuli-responsive block copolymers for multimodal bioimaging

Lizhuang Zhong ^a ,
Ming Liu ^{a, *,} ,
Shilong Su ^a ,
Dongxin Zeng ^a ,
Jing Hu ^{a, b, *,} ,
Zhiqian Guo ^{c, *,}

a.
School of Perfume and Aroma Technology, Shanghai Institute of Technology, Shanghai 201418, China
b.
School of Chemical Engineering, East China University of Science and Technology, Shanghai 200237, China
c.
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa, Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China

mingliu@sit.edu.cn

hujing@ecust.edu.cn

guozq@ecust.edu.cn

Received Date: 13 May 2025
Revised Date: 24 June 2025
Accepted Date: 25 June 2025
Available Online: 25 June 2025

Figures(7)

The diagnostic efficacy of contemporary bioimaging technologies remains constrained by inherent limitations of conventional imaging agents, including suboptimal sensitivity, off-target biodistribution, and inherent cytotoxicity. These limitations have catalyzed the development of intelligent stimuli-responsive block copolymers-based bioimaging agents, which was engineered to dynamically respond to endogenous biochemical cues (e.g., pH gradients, redox potential, enzyme activity, hypoxia environment) or exogenous physical triggers (e.g., photoirradiation, thermal gradients, ultrasound (US)/magnetic stimuli). Through spatiotemporally controlled structural transformations, stimuli-responsive block copolymers enable precise contrast targeting, activatable signal amplification, and theranostic integration, thereby substantially enhancing signal-to-noise ratios of bioimaging and diagnostic specificity. Hence, this mini-review systematically examines molecular engineering principles for designing pH-, redox-, enzyme-, light-, thermo-, and US/magnetic-responsive polymers, with emphasis on structure-property relationships governing imaging performance modulation. Furthermore, we critically analyze emerging strategies for optical imaging, US synergies, and magnetic resonance imaging (MRI). Multimodal bioimaging has also been elaborated, which could overcome the inherent trade-offs between resolution, penetration depth, and functional specificity in single-modal approaches. By elucidating mechanistic insights and translational challenges, this mini-review aims to establish a design framework of stimuli-responsive block copolymers-based for high fidelity bioimaging agents and accelerate their clinical translation in precise diagnosis and therapy.
- Stimuli-responsive,
- Block copolymers,
- Molecular engineering,
- Multimodal bioimaging,
- Diagnosis and therapy
1. [1]
  C.M.T. Tran, P.S. Dinh, J. Biomol. Struct. Dyn. (2024), doi: 10.1080/07391102.2024.2328744. doi: 10.1080/07391102.2024.2328744
2. [2]
  A.G. Robertson, L.M. Rendina, Chem. Soc. Rev. 50 (2021) 4231–4244. doi: 10.1039/d0cs01075h
3. [3]
  T.C. Owens, N. Anton, M.F. Attia, Acta Biomater. 171 (2023) 19–36.
4. [4]
  T. Hu, C. Shen, X. Wang, F. Wu, Z. He, Chin. Chem. Lett. 35 (2024) 109562.
5. [5]
  M. Zhao, Y. Lu, Y. Zhang, H. Xue, Z. Guo, Chin. Chem. Lett. 36 (2025) 110105.
6. [6]
  Y. Shi, Q. Yu, L. Tan, Q. Wang, W.H. Zhu, Angew. Chem. 137 (2025) e202503776.
7. [7]
  Y. Hao, J. Meng, S. Wang, Chin. Chem. Lett. 28 (2017) 2085–2091.
8. [8]
  L. Guerassimoff, M. Ferrere, A. Bossion, J. Nicolas, Chem. Soc. Rev. 53 (2024) 6511–6567. doi: 10.1039/d2cs01060g
9. [9]
  P. Zhang, Y. Wang, J. Lian, et al., Adv. Mater. 29 (2017) 36.
10. [10]
  S.B. Shotorbani, M.M. Hasani Sadrabadi, A. Karkhaneh, et al., J. Control. Release 253 (2017) 46–63.
11. [11]
  Y. Song, H. Jing, L.B. Vong, J. Wang, N. Li, Chin. Chem. Lett. 33 (2022) 1705–1717.
12. [12]
  H. Ding, P. Tan, S. Fu, et al., J. Control. Release 348 (2022) 206–238.
13. [13]
  Y. Zhang, Y. Li, H. Li, et al., Chin. Chem. Lett. 33 (2022) 501–507.
14. [14]
  W.H. Tao, Z.G. He, Asian J. Pharm. Sci. 13 (2018) 101–112.
15. [15]
  Y. Tao, C. Dai, Z. Xie, et al., Chin. Chem. Lett. 35 (2024) 109170.
16. [16]
  S. Wang, K. Yu, Z. Yu, et al., Chin. Chem. Lett. 34 (2023) 108184.
17. [17]
  S. Wang, Y. Liu, Q. Sun, et al., Adv. Sci. 10 (2023) 2303167.
18. [18]
  D. Wei, Y. Sun, H. Zhu, Q. Fu, ACS Nano 17 (2023) 23223–23261. doi: 10.1021/acsnano.3c06019
19. [19]
  Q. Zhang, Y.N. Zhang, Y. Wan, et al., Prog. Polym. Sci. 116 (2021) 34. doi: 10.2979/jmodelite.44.2.04
20. [20]
  B. Ma, J. Shi, Y. Zhang, et al., Adv. Mater. 36 (2024) 2306358.
21. [21]
  B. Zhang, D.R. Lu, D.B.R. Wang, et al., Adv. Funct. Mater. 34 (2024) 2407869.
22. [22]
  D.D. Wang, M. Li, H.N. Zhang, et al., Biomacromolecules 24 (2023) 4303–4315. doi: 10.1021/acs.biomac.3c00702
23. [23]
  K. Li, S. Zhou, Y. Chen, P. Xu, B. Song, Sens. Actuator B: Chem. 363 (2022) 131860.
24. [24]
  H. Zhou, F. Qin, C. Chen, Adv. Healthc. Mater. 10 (2021) 2001277.
25. [25]
  M.Z. Zhu, G. Ren, J.Q. Guo, et al., ACS Appl. Nano Mater. 7 (2024) 12452–12465. doi: 10.1021/acsanm.4c00826
26. [26]
  C. Yan, L. Shi, Z. Guo, W. Zhu, Chin. Chem. Lett. 30 (2019) 1849–1855.
27. [27]
  H. Yang, M. Li, W. Zhao, Z. Guo, W.H. Zhu, Chin. Chem. Lett. 32 (2021) 3882–3885.
28. [28]
  N. Badi, Prog. Polym. Sci. 66 (2016) 54–79.
29. [29]
  A. Abdollahi, H. Roghani-Mamaqani, B. Razavi, M. Salami-Kalajahi, Polym. Chem. 10 (2019) 5686–5720. doi: 10.1039/c9py00890j
30. [30]
  L. Beauté, N. McClenaghan, S. Lecommandoux, Adv. Drug Deliv. Rev. 138 (2019) 148–166.
31. [31]
  Y. Chen, L. Li, G. Han, et al., Chin. Chem. Lett. 36 (2025) 110458.
32. [32]
  X. Xiao, W. Zheng, Y. Zhao, C.H. Li, Chin. Chem. Lett. 34 (2023) 107457.
33. [33]
  L.X. Yu, Y. Liu, S.C. Chen, Y. Guan, Y.Z. Wang, Chin. Chem. Lett. 25 (2014) 389–396.
34. [34]
  F.D. Jochum, P. Theato, Chem. Soc. Rev. 42 (2013) 7468–7483.
35. [35]
  A. Xie, S. Hanif, J. Ouyang, et al., EBioMedicine 56 (2020) 102821.
36. [36]
  X.H. Wang, M.Y. Shan, S.K. Zhang, et al., Adv. Sci. 9 (2022) 2104843.
37. [37]
  F.Q. Wang, G.X. Xia, X.Q. Lang, et al., Colloid Surf. B: Biointerfaces 148 (2016) 147–156.
38. [38]
  A. Zhang, K. Jung, A. Li, J. Liu, C. Boyer, Prog. Polym. Sci. 99 (2019) 101164.
39. [39]
  H. Cui, W. Zhu, C. Yue, et al., Chin. Chem. Lett. 35 (2024) 109727.
40. [40]
  J. Thevenot, H. Oliveira, O. Sandre, S. Lecommandoux, Chem. Soc. Rev. 42 (2013) 7099–7116. doi: 10.1039/c3cs60058k
41. [41]
  H. Cai, X.H. Dai, X.M. Wang, et al., Adv. Sci. 7 (2020) 1903243.
42. [42]
  S. Chen, B. Sun, H. Miao, et al., ACS Mater. Lett. 2 (2020) 174–183.
43. [43]
  D. Tang, M. Cui, B. Wang, et al., Nat. Commun. 15 (2024) 6026.
44. [44]
  S.S. Das, P. Bharadwaj, M. Bilal, et al., Polymers 12 (2020) 1397. doi: 10.3390/polym12061397
45. [45]
  P. Wei, E.J. Cornel, J.Z. Du, Drug Deliv. Transl. Res. 11 (2021) 1323–1339. doi: 10.1007/s13346-021-00963-0
46. [46]
  J.B. Gao, B.Q. Yu, C. Li, et al., Colloid Surf. B: Biointerfaces 174 (2019) 416–425.
47. [47]
  E. Jung, J. Noh, C. Kang, et al., Biomaterials 179 (2018) 175–185.
48. [48]
  J. Lin, X.Y. Chen, Y. Li, et al., Mater. Today Bio 26 (2024) 101037.
49. [49]
  B. Chen, L. Liu, R. Yue, et al., Nano Today 51 (2023) 101931.
50. [50]
  T.A. Tunca Arın, O. Sedlacek, Biomacromolecules 25 (2024) 5630–5649. doi: 10.1021/acs.biomac.4c00833
51. [51]
  A. Usman, C. Zhang, J.C. Zhao, et al., Polym. Chem. 12 (2021) 5438–5448. doi: 10.1039/d1py00602a
52. [52]
  H. Xiao, X. Li, C. Zheng, et al., J. Nanopart. Res. 22 (2020) 105.
53. [53]
  M. Shen, H. Jiang, S. Li, et al., J. Mater. Chem. B 12 (2024) 1344–1354. doi: 10.1039/d3tb00407d
54. [54]
  C. Huang, Y. Qin, S. Wu, et al., Nano Lett. 24 (2024) 9561–9568. doi: 10.1021/acs.nanolett.4c02137
55. [55]
  P. Wang, Z. Peng, Y.Y. Zhang, et al., Carbohydr. Polym. 335 (2024) 122073.
1. [1]
  Huan Hu , Ying Zhang , Shi-Shuang Huang , Zhi-Gang Li , Yungui Liu , Rui Feng , Wei Li . Temperature- and pressure-responsive photoluminescence in a 1D hybrid lead halide. Chinese Journal of Structural Chemistry, 2024, 43(10): 100395-100395. doi: 10.1016/j.cjsc.2024.100395
2. [2]
  Dongpu Wu , Zheng Yang , Yuchen Xia , Lulu Wu , Yingxia Zhou , Caoyuan Niu , Puhui Xie , Xin Zheng , Zhanqi Cao . Surface controllable wettability using amphiphilic rotaxane molecular shuttles. Chinese Chemical Letters, 2025, 36(2): 110353-. doi: 10.1016/j.cclet.2024.110353
3. [3]
  Qiangwei Wang , Huijiao Liu , Mengjie Wang , Haojie Zhang , Jianda Xie , Xuanwei Hu , Shiming Zhou , Weitai Wu . Observation of high ionic conductivity of polyelectrolyte microgels in salt-free solutions. Chinese Chemical Letters, 2024, 35(4): 108743-. doi: 10.1016/j.cclet.2023.108743
4. [4]
  Fanghua Zhang , Yuyan Li , Hongyan Zhang , Wendong Liu , Zhe Hao , Mingzheng Shao , Ruizhong Zhang , Xiyan Li , Libing Zhang . Logically integrating exo/endogenous gated DNA trackers for precise microRNA imaging via synergistic manipulation. Chinese Chemical Letters, 2025, 36(1): 109848-. doi: 10.1016/j.cclet.2024.109848
5. [5]
  Yaqiong Kong , Yan Su , Yong Qian , Robert J. Deeth , Isolda Romero-Canelón , Zhi Su , Hong-Ke Liu , Peter J. Sadler . Unusual dynamic stimuli-responsive metallamacrocyclic configurational switches. Chinese Chemical Letters, 2026, 37(3): 111375-. doi: 10.1016/j.cclet.2025.111375
6. [6]
  Jialiang XU , Jiabin CUI . Recent biological applications of corroles: From diagnosis to therapy. Chinese Journal of Inorganic Chemistry, 2024, 40(12): 2303-2317. doi: 10.11862/CJIC.20240245
7. [7]
  Yubo Tan , Ziying Wang , Yibo An , Man Li , Dazhuang Xu , Renyuan Liu , Xinyu Tan , Yaohui He , Zhixiang Lu , Gang Liu . Molecular engineering organometallic sonosensitizer for enhanced sonodynamic therapy via promoting ER stress-mediated HIF-1α degradation and cGAS-STING pathway activation. Chinese Chemical Letters, 2026, 37(3): 111214-. doi: 10.1016/j.cclet.2025.111214
8. [8]
  Hongwei Ding , Jingjing Yang , Yongchen Shuai , Di Wei , Xueliang Liu , Guiying Li , Lin Jin , Jianliang Shen . In situ preparation of tannin-mediated CeO₂@CuS nanocomposites for multimodal wound therapy. Chinese Chemical Letters, 2025, 36(6): 110286-. doi: 10.1016/j.cclet.2024.110286
9. [9]
  Hui Guo , Wen-Wen Li , Mei-Yin Wu , Jian-Bo Hu , Jun Wang , Yun Liu , Yang Zou , Chu-Luo Yang , Kai-Lu Zheng . Indolizine-benzophenone hybrid acceptors enable TADF materials for bioimaging and photodynamic therapy in living cells. Chinese Chemical Letters, 2026, 37(1): 111721-. doi: 10.1016/j.cclet.2025.111721
10. [10]
  Wenjie Zhang , Jiong Zhou . Enhanced oxygen reduction through axial chlorine engineering of p-block antimony atomic sites. Chinese Journal of Structural Chemistry, 2026, 45(1): 100732-100732. doi: 10.1016/j.cjsc.2025.100732
11. [11]
  Hong-Guang Fu , Xuan Wu , Hui-Juan Wang , Fanjun Zhang , Yong Chen , Jing Xu . Color-tunable multi-stimuli-responsive luminescent system based on diarylethene and photoacid. Chinese Chemical Letters, 2025, 36(8): 110741-. doi: 10.1016/j.cclet.2024.110741
12. [12]
  Zhiyao Yang , Kuirong Fu , Wentao Yu , Along Jia , Xinnan Chen , Yimin Cai , Xiaowei Li , Wen Feng , Lihua Yuan . A multi-stimuli responsive [3]rotaxane based on hydrogen-bonded aramide azo-macrocycles. Chinese Chemical Letters, 2025, 36(9): 110842-. doi: 10.1016/j.cclet.2025.110842
13. [13]
  Yajie Yang , Mengde Zhai , Haoxin Wang , Cheng Chen , Ziyang Xia , Chengyang Liu , Yi Tian , Ming Cheng . Molecular engineering of dibenzo-heterocyclic core based hole-transporting materials for perovskite solar cells. Chinese Chemical Letters, 2025, 36(5): 110700-. doi: 10.1016/j.cclet.2024.110700
14. [14]
  Yaojun Li , Yun Li , Shenglong Liao , Yang Li , Shouchun Yin . Revolutionizing cancer therapies with organic photovoltaic non-fullerene acceptors: A deep dive into molecular engineering for advanced phototheranostics. Chinese Chemical Letters, 2025, 36(8): 110832-. doi: 10.1016/j.cclet.2025.110832
15. [15]
  Lizhi Wang , Chuanxin Wei , Xinyu Du , Yingying Zheng , Shuang Li , Ning Sun , Zhiqiang Zhuo , Ningning Yu , Yingru Lin , Zhiyang Sun , Jinyi Lin , Man Xu , Yongzheng Chang , Tianshi Qin , Zhoulu Wang , Xuehua Ding , Wei Huang . Energy engineering and mechanical elasticity of molecular crystals via supramolecular salt strategy for flexible visible optical waveguide. Chinese Chemical Letters, 2026, 37(2): 111634-. doi: 10.1016/j.cclet.2025.111634
16. [16]
  Li Qin , Wenjing Wei , Keqing Wang , Xianbao Shi , Guixia Ling , Peng Zhang . Ultrasound-responsive heterojunction sonosensitizers for multifunctional synergistic sonodynamic therapy. Chinese Chemical Letters, 2025, 36(7): 110777-. doi: 10.1016/j.cclet.2024.110777
17. [17]
  Xinran Xi , Xiyu Wang , Ziyue Xi , Chuanyong Fan , Yingying Jiang , Zhenhua Li , Lu Xu . Facile GSH responsive glycyrrhetinic acid conjunction for liver targeting therapy. Chinese Chemical Letters, 2025, 36(10): 110773-. doi: 10.1016/j.cclet.2024.110773
18. [18]
  Zhaoyong Kang , Shen Li , Yan Li , Jingfeng Song , Yangrui Peng , Yihua Chen . Small molecular inhibitors and degraders targeting STAT3 for cancer therapy: An updated review (from 2022 to 2024). Chinese Chemical Letters, 2025, 36(7): 110447-. doi: 10.1016/j.cclet.2024.110447
19. [19]
  Wei Zhou , Di He , Ning Liu , Ying Li , Wenzhao Han , Weiping Zhou , Siyu Zhang , Cong Yu . A PDI-based NIR-Ⅱ fluorescence imaging guided molecular phototheranostic platform for GSH-triggered gas therapy, mild photothermal therapy and NIR-activated photodynamic therapy. Chinese Chemical Letters, 2025, 36(11): 110854-. doi: 10.1016/j.cclet.2025.110854
20. [20]
  Mao-Fan Li , Ming‐Yu Guo , De-Xuan Liu , Xiao-Xian Chen , Wei-Jian Xu , Wei-Xiong Zhang . Multi-stimuli responsive behaviors in a new chiral hybrid nitroprusside salt (R-3-hydroxypyrrolidinium)₂[Fe(CN)₅(NO)]. Chinese Chemical Letters, 2024, 35(12): 109507-. doi: 10.1016/j.cclet.2024.109507

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(859)
HTML views(68)

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