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Modulating planarity of cyanine dye to construct highly stable H-aggregates for enhanced photothermal therapy

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Abstract

Self-assembly of dyes has become a flexible strategy to modulate their photophysical properties. H-aggregates show great potential to increase heat generation, while the precise designing of H-aggregates as efficient photothermal agents is still challenging. Herein, a quinoline cyanine (QCy) is developed for constructing stable H-aggregated nanoparticles (NPs) to significantly enhance photostability and photothermal conversion efficiency (PCE). With symmetrical rigid planar quinoline structures, QCy has a small and symmetrical dihedral angle (11.9°), which ensures excellent molecular planarity. In aqueous solution, the planar QCy can form close π−π molecular stacking, and fast self-assemble into stable H-aggregates even at low concentrations (1 × 10−7 M). QCy H-aggregates are sphere-like NPs (QCy NPs) with an average diameter of 120 nm and exhibit high stability. H-aggregation of QCy significantly enhances PCE from 20.1% (non-H-aggregated QCy) to 63.8% (QCy NPs). In addition, the positive charge of quaternarized quinoline provides mitochondrial anchoring ability, which further enhances the photothermal effect. With high PCE and tumor accumulation, QCy NPs in low-doses have been successfully used in photoacoustic imaging-guided tumor photothermal therapy.

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References

  1. Sun, R.; Liu, M. Z.; Xu, Z. J.; Song, B.; He, Y.; Wang, H. Y. Silicon-based nanoprobes cross the blood-brain barrier for photothermal therapy of glioblastoma. Nano Res. 2022, 15, 7392–7401.

    Article  CAS  Google Scholar 

  2. Liu, Y. J.; Bhattarai, P.; Dai, Z. F.; Chen, X. Y. Photothermal therapy and photoacoustic imaging via nanotheranostics in fighting cancer. Chem. Soc. Rev. 2019, 48, 2053–2108.

    Article  CAS  Google Scholar 

  3. Sun, H. T.; Zhang, Q.; Li, J. C.; Peng, S. J.; Wang, X. L.; Cai, R. Near-infrared photoactivated nanomedicines for photothermal synergistic cancer therapy. Nano Today 2021, 37, 101073.

    Article  CAS  Google Scholar 

  4. Xu, C.; Pu, K. Y. Second near-infrared photothermal materials for combinational nanotheranostics. Chem. Soc. Rev. 2021, 50, 1111–1137.

    Article  CAS  Google Scholar 

  5. Ji, C. D.; Cheng, W. Y.; Hu, Y. S.; Liu, Y. F.; Liu, F. Y.; Yin, M. Z. A nano vector with photothermally enhanced drug release and retention to overcome cancer multidrug resistance. Nano Today 2021, 36, 101020.

    Article  CAS  Google Scholar 

  6. Wang, H. Y.; Chang, J. J.; Shi, M. W.; Pan, W.; Li, N.; Tang, B. A dual-targeted organic photothermal agent for enhanced photothermal therapy. Angew. Chem., Int. Ed. 2019, 58, 1057–1061.

    Article  CAS  Google Scholar 

  7. Ni, J. S.; Zhang, X.; Yang, G.; Kang, T. Y.; Lin, X. W.; Zha, M.; Li, Y. X.; Wang, L. D.; Li, K. A photoinduced nonadiabatic decay-guided molecular motor triggers effective photothermal conversion for cancer therapy. Angew. Chem., Int. Ed. 2020, 59, 11298–11302.

    Article  CAS  Google Scholar 

  8. Zhen, X.; Pu, K. Y.; Jiang, X. Q. Photoacoustic imaging and photothermal therapy of semiconducting polymer nanoparticles: Signal amplification and second near-infrared construction. Small 2021, 17, 2004723.

    Article  CAS  Google Scholar 

  9. Zhang, S. B.; Guo, W. S.; Wei, J.; Li, C.; Liang, X. J.; Yin, M. Z. Terrylenediimide-based intrinsic theranostic nanomedicines with high photothermal conversion efficiency for photoacoustic imaging-guided cancer therapy. ACS Nano 2017, 11, 3797–3805.

    Article  CAS  Google Scholar 

  10. Liu, C.; Zhang, S. B.; Li, J. H.; Wei, J.; Müllen, K.; Yin, M. Z. A water-soluble, NIR-absorbing quaterrylenediimide chromophore for photoacoustic imaging and efficient photothermal cancer therapy. Angew. Chem., Int. Ed. 2019, 58, 1638–1642.

    Article  CAS  Google Scholar 

  11. Shi, N. N.; Shi, Y. H.; Shao, J. W.; Yang, X.; Zhang, X. L.; Zhang, Y.; Warsame, U. F.; Shao, J. J.; Dong, X. C. Selenadiazolobenzotriazole based near infrared dyes with enhanced intramolecular charge transfer and photothermal effect: Synthesis, characterization and photophysical properties. Dyes Pigm. 2019, 160, 683–691.

    Article  CAS  Google Scholar 

  12. Li, J. H.; Liu, C.; Hu, Y. S.; Ji, C. D.; Li, S. L.; Yin, M. Z. pH-responsive perylenediimide nanoparticles for cancer trimodality imaging and photothermal therapy. Theranostics 2020, 10, 166–178.

    Article  CAS  Google Scholar 

  13. Hu, W. B.; Miao, X. F.; Tao, H. J.; Baev, A.; Ren, C.; Fan, Q. L.; He, T. C.; Huang, W.; Prasad, P. N. Manipulating nonradiative decay channel by intermolecular charge transfer for exceptionally improved photothermal conversion. ACS Nano 2019, 13, 12006–12014.

    Article  CAS  Google Scholar 

  14. Xi, D. M.; Xiao, M.; Cao, J. F.; Zhao, L. Z.; Xu, N.; Long, S. R.; Fan, J. L.; Shao, K.; Sun, W.; Yan, X. H. et al. NIR light-driving barrier-free group rotation in nanoparticles with an 88.3% photothermal conversion efficiency for photothermal therapy. Adv. Mater. 2020, 32, 1907855.

    Article  CAS  Google Scholar 

  15. Liu, S. J.; Zhou, X.; Zhang, H. K.; Ou, H. L.; Lam, J. W. Y.; Liu, Y.; Shi, L. Q.; Ding, D.; Tang, B. Z. Molecular motion in aggregates: Manipulating TICT for boosting photothermal theranostics. J. Am. Chem. Soc. 2019, 141, 5359–5368.

    Article  CAS  Google Scholar 

  16. Ji, C. D.; Gao, Q.; Dong, X. H.; Yin, W. Y.; Gu, Z. J.; Gan, Z. H.; Zhao, Y. L.; Yin, M. Z. A size-reducible nanodrug with an aggregation-enhanced photodynamic effect for deep chemophotodynamic therapy. Angew. Chem., Int. Ed. 2018, 57, 11384–11388.

    Article  CAS  Google Scholar 

  17. Zhao, L. Y.; Liu, Y. M.; Xing, R. R.; Yan, X. H. Supramolecular photothermal effects: A promising mechanism for efficient thermal conversion. Angew. Chem., Int. Ed. 2020, 59, 3793–3801.

    Article  CAS  Google Scholar 

  18. Zou, Q. L.; Abbas, M.; Zhao, L. Y.; Li, S. K.; Shen, G. Z.; Yan, X. H. Biological photothermal nanodots based on self-assembly of peptide-porphyrin conjugates for antitumor therapy. J. Am. Chem. Soc. 2017, 139, 1921–1927.

    Article  CAS  Google Scholar 

  19. Lyu, Y.; Zeng, J. F.; Jiang, Y. Y.; Zhen, X.; Wang, T.; Qiu, S. S.; Lou, X.; Gao, M. Y.; Pu, K. Y. Enhancing both biodegradability and efficacy of semiconducting polymer nanoparticles for photoacoustic imaging and photothermal therapy. ACS Nano 2018, 12, 1801–1810.

    Article  CAS  Google Scholar 

  20. Ji, C. D.; Lai, L. M.; Li, P. Y.; Wu, Z.; Cheng, W. Y.; Yin, M. Z. Organic dye assemblies with aggregation-induced photophysical changes and their bio-applications. Aggregate 2021, 2, e39.

    Google Scholar 

  21. Jiang, Z. Q.; Yuan, B.; Wang, Y. J.; Wei, Z. N.; Sun, S.; Akakuru, O. U.; Li, Y.; Li, J.; Wu, A. G. Near-infrared heptamethine cyanine dye-based nanoscale coordination polymers with intrinsic nucleus-targeting for low temperature photothermal therapy. Nano Today 2020, 34, 100910.

    Article  CAS  Google Scholar 

  22. Shi, M. W.; Fu, Z. L.; Pan, W.; Chen, Y. Y.; Wang, K. Y.; Zhou, P.; Li, N.; Tang, B. A protein-binding molecular photothermal agent for tumor ablation. Angew. Chem., Int. Ed. 2021, 60, 13564–13568.

    Article  CAS  Google Scholar 

  23. Mu, X.; Lu, Y. X.; Wu, F. P.; Wei, Y. H.; Ma, H. H.; Zhao, Y. J.; Sun, J.; Liu, S. F.; Zhou, X. F.; Li, Z. B. Supramolecular nanodiscs self-assembled from non-ionic heptamethine cyanine for imaging-guided cancer photothermal therapy. Adv. Mater. 2020, 32, 1906711.

    Article  CAS  Google Scholar 

  24. Jung, H. S.; Lee, J. H.; Kim, K.; Koo, S.; Verwilst, P.; Sessler, J. L.; Kang, C.; Kim, J. S. A mitochondria-targeted cryptocyanine-based photothermogenic photosensitizer. J. m. Chem. Soc. 2017, 139, 9972–9978.

    Article  CAS  Google Scholar 

  25. Zhao, X. Z.; Long, S. R.; Li, M. L.; Cao, J. F.; Li, Y. C.; Guo, L. Y.; Sun, W.; Du, J. J.; Fan, J. L.; Peng, X. J. Oxygen-dependent regulation of excited-state deactivation process of rational photosensitizer for smart phototherapy. J. Am. Chem. Soc. 2020, 142, 1510–1517.

    Article  CAS  Google Scholar 

  26. Wang, Y. F.; Du, W.; Zhang, T.; Zhu, Y.; Ni, Y. H.; Wang, C. C.; Raya, F. M. S.; Zou, L. W.; Wang, L. S.; Liang, G. L. A self-evaluating photothermal therapeutic nanoparticle. ACS Nano 2020, 14, 9585–9593.

    Article  CAS  Google Scholar 

  27. Wan, J. X.; Sun, L. Y.; Wu, P.; Wang, F.; Guo, J.; Cheng, J. J.; Wang, C. C. Synthesis of indocyanine green functionalized comblike poly(aspartic acid) derivatives for enhanced cancer cell ablation by targeting the endoplasmic reticulum. Polym. Chem. 2018, 9, 1206–1215.

    Article  CAS  Google Scholar 

  28. Deng, Y. B.; Huang, L.; Yang, H.; Ke, H. T.; He, H.; Guo, Z. Q.; Yang, T.; Zhu, A. J.; Wu, H.; Chen, H. B. Cyanine-anchored silica nanochannels for light-driven synergistic thermo-chemotherapy. Small 2017, 13, 1602747.

    Article  Google Scholar 

  29. Chen, W.; Cheng, C. A.; Cosco, E. D.; Ramakrishnan, S.; Lingg, J. G. P.; Bruns, O. T.; Zink, J. I.; Sletten, E. M. Shortwave infrared imaging with J-aggregates stabilized in hollow mesoporous silica nanoparticles. J. Am. Chem. Soc. 2019, 141, 12475–12480.

    Article  CAS  Google Scholar 

  30. Song, X. J.; Zhang, R.; Liang, C.; Chen, Q.; Gong, H.; Liu, Z. Nano-assemblies of J-aggregates based on a NIR dye as a multifunctional drug carrier for combination cancer therapy. Biomaterials 2015, 57, 84–92.

    Article  CAS  Google Scholar 

  31. Bricks, J. L.; Slominskii, Y. L.; Panas, I. D.; Demchenko, A. P. Fluorescent J-aggregates of cyanine dyes: Basic research and applications review. Methods Appl. Fluoresc. 2017, 6, 012001.

    Article  Google Scholar 

  32. Heyne, B. Self-assembly of organic dyes in supramolecular aggregates. Photochem. Photobiol. Sci. 2016, 15, 1103–1114.

    Article  CAS  Google Scholar 

  33. Hestand, N. J.; Spano, F. C. Expanded theory of H- and J-molecular aggregates: The effects of vibronic coupling and intermolecular charge transfer. Chem. Rev. 2018, 118, 7069–7163.

    Article  CAS  Google Scholar 

  34. Zheng, R.; Yang, J.; Mamuti, M.; Hou, D. Y.; An, H. W.; Zhao, Y. L.; Wang, H. Controllable self-assembly of peptide-cyanine conjugates in vivo as fine-tunable theranostics. Angew. Chem., Int. Ed. 2021, 60, 7809–7819.

    Article  CAS  Google Scholar 

  35. Wang, Y. G.; Xia, G. M.; Tan, M. M.; Wang, M. D.; Li, Y. Z.; Wang, H. M. H-dimeric nanospheres of amphipathic squaraine dye with an 81.2% photothermal conversion efficiency for photothermal therapy. Adv. Funct. Mater. 2022, 32, 2113098.

    Article  CAS  Google Scholar 

  36. Li, X. J.; Yang, M. W.; Cao, J. F.; Gu, H.; Liu, W. J.; Xia, T. P.; Sun, W.; Fan, J. L.; Peng, X. J. H-aggregates of prodrughemicyanine conjugate for enhanced photothermal therapy and sequential hypoxia-activated chemotherapy. ACS Materials Lett. 2022, 4, 724–732.

    Article  CAS  Google Scholar 

  37. Wu, F. P.; Lu, Y. X.; Mu, X. L. E.; Chen, Z. T.; Liu, S. S.; Zhou, X. F.; Liu, S. F.; Li, Z. B. Intriguing H-aggregates of heptamethine cyanine for imaging-guided photothermal cancer therapy. ACS Appl. Mater. Interfaces 2020, 12, 32388–32396.

    Article  CAS  Google Scholar 

  38. Wang, B. L.; Jiang, C. DNA G-quadruplexes as a template to direct cyanine dyes to form H-aggregates and application of the self-assembly entity as a new G-quadruplexes ligands screening platform. Anal. Chem. 2019, 91, 1541–1547.

    Article  CAS  Google Scholar 

  39. Nicoli, F.; Roos, M. K.; Hemmig, E. A.; Di Antonio, M.; De Vivie-Riedle, R.; Liedl, T. Proximity-induced H-aggregation of cyanine dyes on DNA-duplexes. J. Phys. Chem. A 2016, 120, 9941–9947.

    Article  CAS  Google Scholar 

  40. Tsai, W. W.; Tevis, I. D.; Tayi, A. S.; Cui, H. G.; Stupp, S. I. Semiconducting nanowires from hairpin-shaped self-assembling sexithiophenes. J. Phys. Chem. B 2010, 114, 14778–14786.

    Article  CAS  Google Scholar 

  41. Li, Z.; Mukhopadhyay, S.; Jang, S. H.; Brédas, J. L.; Jen, A. K. Y. Supramolecular assembly of complementary cyanine salt J-aggregates. J. Am. Chem. Soc. 2015, 137, 11920–11923.

    Article  CAS  Google Scholar 

  42. Cai, Y.; Ni, D. Q.; Cheng, W. Y.; Ji, C. D.; Wang, Y. L.; Müllen, K.; Su, Z. Q.; Liu, Y.; Chen, C. Y.; Yin, M. Z. Enzyme-triggered disassembly of perylene monoimide-based nanoclusters for activatable and deep photodynamic therapy. Angew. Chem., Int. Ed. 2020, 59, 14014–14018.

    Article  CAS  Google Scholar 

  43. Pleckaitis, M.; Habach, F.; Kontenis, L.; Steinbach, G.; Jarockyte, G.; Kalnaityte, A.; Domonkos, I.; Akhtar, P.; Alizadeh, M.; Bagdonas, S. Structure and principles of self-assembly of giant “sea urchin” type sulfonatophenyl porphine aggregates. Nano Res. 2022, 15, 5527–5537.

    Article  CAS  Google Scholar 

  44. Zou, Y.; Li, M. L.; Xiong, T.; Zhao, X. Z.; Du, J. J.; Fan, J. L.; Peng, X. J. A single molecule drug targeting photosensitizer for enhanced breast cancer photothermal therapy. Small 2020, 16, 1907677.

    Article  CAS  Google Scholar 

  45. Li, C. N.; Zhang, W.; Liu, S.; Hu, X. L.; Xie, Z. G. Mitochondria-targeting organic nanoparticles for enhanced photodynamic/photothermal therapy. ACS Appl. Mater. Interfaces 2020, 12, 30077–30084.

    Article  CAS  Google Scholar 

  46. Zhang, Y. Y.; Li, Z.; Hu, W.; Liu, Z. H. A mitochondrial-targeting near-infrared fluorescent probe for visualizing and monitoring viscosity in live cells and tissues. Anal. Chem. 2019, 91, 10302–10309.

    Article  CAS  Google Scholar 

  47. Wang, K. N.; Liu, L. Y.; Qi, G. B.; Chao, X. J.; Ma, W.; Yu, Z. Q.; Pan, Q. L.; Mao, Z. W.; Liu, B. Light-driven cascade mitochondria-to-nucleus photosensitization in cancer cell ablation. Adv. Sci. 2021, 8, 2004379.

    Article  CAS  Google Scholar 

  48. Kim, K. Y.; Jin, H. Y.; Park, J.; Jung, S. H.; Lee, J. H.; Park, H.; Kim, S. K.; Bae, J.; Jung, J. H. Mitochondria-targeting self-assembled nanoparticles derived from triphenylphosphonium-conjugated cyanostilbene enable site-specific imaging and anticancer drug delivery. Nano Res. 2018, 11, 1082–1098.

    Article  CAS  Google Scholar 

  49. Yuan, P.; Ruan, Z.; Yan, L. F. Tetraphenylporphine-modified polymeric nanoparticles containing NIR photosensitizer for mitochondria-targeting and imaging-guided photodynamic therapy. ACS Biomater. Sci. Eng. 2020, 6, 1043–1051.

    Article  CAS  Google Scholar 

  50. Pan, T.; Fu, W.; Xin, H. B.; Geng, S. Y.; Li, Z. B.; Cui, H. D.; Zhang, Y. L.; Chu, P. K.; Zhou, W. H.; Yu, X. F. Calcium phosphate mineralized black phosphorous with enhanced functionality and anticancer bioactivity. Adv. Funct. Mater. 2020, 30, 2003069.

    Article  CAS  Google Scholar 

  51. Liu, J. P.; Sun, L. Y.; Li, L.; Zhang, R.; Xu, Z. P. Synergistic cancer photochemotherapy via layered double hydroxide-based trimodal nanomedicine at very low therapeutic doses. ACS Appl. Mater. Interfaces 2021, 13, 7115–7126.

    Article  CAS  Google Scholar 

  52. Bian, W. Q.; Pan, Z. X.; Wang, Y. K.; Long, W.; Chen, Z. F.; Chen, N. P.; Zeng, Y. X.; Yuan, J. P.; Liu, X. J.; Lu, Y. J. et al. A mitochondria-targeted thiazoleorange-based photothermal agent for enhanced photothermal therapy for tumors. Bioorg. Chem. 2021, 113, 104954.

    Article  CAS  Google Scholar 

  53. Liu, R. F.; Tang, J.; Xu, Y. X.; Zhou, Y. M.; Dai, Z. F. Nano-sized indocyanine green J-aggregate as a one-component theranostic agent. Nanotheranostics 2017, 1, 430–439.

    Article  Google Scholar 

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Nos. 52130309 and 51903014), Beijing Natural Science Foundation (No. 2202043), and Changzhou Sci&Tech Program (No. CJ20210041). All animal procedures were performed in accordance with the Guidelines for Care and Use of Laboratory Animals of Peking Union Medical College and approved by the Animal Ethics Committee of the Ethical Committee of Peking Union Medical College.

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  1. State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China

    Kai Wei, Yanxin Wu, Pengyu Li, Xian Zheng, Chendong Ji & Meizhen Yin

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  1. Kai Wei
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  2. Yanxin Wu
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  3. Pengyu Li
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  4. Xian Zheng
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Correspondence to Chendong Ji or Meizhen Yin.

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Wei, K., Wu, Y., Li, P. et al. Modulating planarity of cyanine dye to construct highly stable H-aggregates for enhanced photothermal therapy. Nano Res. 16, 970–979 (2023). https://doi.org/10.1007/s12274-022-4818-0

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  • DOI: https://doi.org/10.1007/s12274-022-4818-0

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