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Vol. 16 (2024)

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-II Photo-Immunotherapy of Metastatic Tumor

https://doi.org/10.1007/s40820-023-01219-x
Yijian Gao
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
Ying Liu
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
Xiliang Li
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
Hui Wang
Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou 215123, People’s Republic of China
Yuliang Yang
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
Yu Luo
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
Yingpeng Wan
Center of Super‑Diamond and Advanced Films (COSDAF) & Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People’s Republic of China
Chun‑sing Lee
Center of Super‑Diamond and Advanced Films (COSDAF) & Department of Chemistry, City University of Hong Kong, 83 Tat Chee Avenue, Kowloon, Hong Kong SAR, People’s Republic of China
Shengliang Li
College of Pharmaceutical Sciences, Soochow University, Suzhou 215123, People’s Republic of China
Xiao‑Hong Zhang
Institute of Functional Nano & Soft Materials (FUNSOM), Soochow University, Suzhou 215123, People’s Republic of China

Corresponding Author: Xiao‑Hong Zhang

xiaohong_zhang@suda.edu.cn

Nano-Micro Letters, Vol. 16 (2024), Article Number: 21

Abstract

Massive efforts have been concentrated on the advance of eminent near-infrared (NIR) photothermal materials (PTMs) in the NIR-II window (1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-II-responsive organic PTMs was explored, and their photothermal conversion efficiencies (PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-II window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-II absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-II light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-II window, without any side-effect. Moreover, by combining with PD-1 antibody, the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-II window, offering a new horizon in developing radical-characteristic NIR-II photothermal materials.


Highlights:
1 By employing side-chain regulation, the photothermal therapy response of conjugated diradical polymer can red-shift from near-infrared (NIR)-I to the NIR-II region. This strategy offers new radical materials in developing NIR-II photothermal materials.
2 The conjugated diradical polymer TTB-2 receives a record-high photothermal conversion efficiency of 87.7%, far beyond the recently reported NIR-II photothermal agents. Such conjugated diradical polymer must enrich the NIR-II photothermal agents’ library and provide important insight for more diradical polymer construction.
3 The conjugated diradical polymer nanoparticles TTB-2 NPs achieve good tumor photoablation with navigation of photoacoustic imaging in the NIR-II window, without any side effect. Furthermore, the efficient photo-immunity effect prevents the pulmonary metastasis of breast cancer.

Keywords

NIR-II conjugated polymer Photothermal Radical Nanoparticles Cancer therapy
Gao, Yijian, Ying Liu, Xiliang Li, Hui Wang, Yuliang Yang, Yu Luo, Yingpeng Wan, Chun‑sing Lee, Shengliang Li, and Xiao‑Hong Zhang. 2023. “A Stable Open-Shell Conjugated Diradical Polymer With Ultra-High Photothermal Conversion Efficiency for NIR-II Photo-Immunotherapy of Metastatic Tumor”. Nano-Micro Letters 16 (November):21. https://doi.org/10.1007/s40820-023-01219-x.
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References
  1. J. Li, L. Xie, B. Li, C. Yin, G. Wang et al., Engineering a hydrogen-sulfide-based nanomodulator to normalize hyperactive photothermal immunogenicity for combination cancer therapy. Adv. Mater. 33(22), e2008481 (2021). https://doi.org/10.1002/adma.202008481
  2. Y. Jiang, J. Huang, C. Xu, K. Pu, Activatable polymer nanoagonist for second near-infrared photothermal immunotherapy of cancer. Nat. Commun. 12(1), 742 (2021). https://doi.org/10.1038/s41467-021-21047-0
  3. Y. Li, Y. Tang, W. Hu, Z. Wang, X. Li et al., Incorporation of robust NIR-II fluorescence brightness and photothermal performance in a single large π-conjugated molecule for phototheranostics. Adv. Sci. 10(3), 2204695 (2022). https://doi.org/10.1002/advs.202204695
  4. K. Wang, Y. Li, X. Wang, Z. Zhang, L. Cao et al., Gas therapy potentiates aggregation-induced emission luminogen-based photoimmunotherapy of poorly immunogenic tumors through cgas-sting pathway activation. Nat. Commun. 14(1), 2950 (2023). https://doi.org/10.1038/s41467-023-38601-7
  5. J. Li, Y. Luo, K. Pu, Electromagnetic nanomedicines for combinational cancer immunotherapy. Angew. Chem. Int. Ed. 60(23), 12682–12705 (2021). https://doi.org/10.1002/anie.202008386
  6. X. Wei, C. Zhang, S. He, J. Huang, J. Huang et al., A dual-locked activatable phototheranostic probe for biomarker-regulated photodynamic and photothermal cancer therapy. Angew. Chem. Int. Ed. 61(26), e202202966 (2022). https://doi.org/10.1002/anie.202202966
  7. X. Hu, N. Wang, X. Guo, Z. Liang, H. Sun et al., A sub-nanostructural transformable nanozyme for tumor photocatalytic therapy. Nano-Micro Lett. 14, 101 (2022). https://doi.org/10.1007/s40820-022-00848-y
  8. C. Xu, Y. Jiang, Y. Han, K. Pu, R. Zhang, A polymer multicellular nanoengager for synergistic NIR-II photothermal immunotherapy. Adv. Mater. 33(14), e2008061 (2021). https://doi.org/10.1002/adma.202008061
  9. Y. Xia, S. Fu, Q. Ma, Y. Liu, N. Zhang, Application of nano-delivery systems in lymph nodes for tumor immunotherapy. Nano-Micro Lett. 15, 145 (2023). https://doi.org/10.1007/s40820-023-01125-2
  10. H. Feng, Y. Yuan, Y. Zhang, H.-J. Liu, X. Dong et al., Targeted micellar phthalocyanine for lymph node metastasis homing and photothermal therapy in an orthotopic colorectal tumor model. Nano-Micro Lett. 13, 145 (2021). https://doi.org/10.1007/s40820-021-00666-8
  11. Z. Huang, Y. Liu, S. Li, C.-S. Lee, X.H. Zhang, From materials to devices: rationally designing solar steam system for advanced applications. Small Methods 6(10), e2200835 (2022). https://doi.org/10.1002/smtd.202200835
  12. J. Zhang, Y. Li, M. Jiang, H. Qiu, Y. Li et al., Self-assembled aza-bodipy and iron(iii) nanops for photothermal-enhanced chemodynamic therapy in the NIR-II window. ACS Biomater. Sci. Eng. 9(2), 821–830 (2023). https://doi.org/10.1021/acsbiomaterials.2c01539
  13. N. Song, Z. Zhang, P. Liu, D. Dai, C. Chen et al., Pillar[5]arene-modified gold nanorods as nanocarriers for multi-modal imaging-guided synergistic photodynamic-photothermal therapy. Adv. Funct. Mater. 31(21), 2009924 (2021). https://doi.org/10.1002/adfm.202009924
  14. M. Fu, Y. Shen, H. Zhou, X. Liu, W. Chen et al., Gallium-based liquid metal micro/nanops for photothermal cancer therapy. J. Mater. Sci. Technol. 142, 22–33 (2023). https://doi.org/10.1016/j.jmst.2022.08.049
  15. B. Chen, C. Zhang, W. Wang, Z. Chu, Z. Zha et al., Ultrastable AgBis(2) hollow nanospheres with cancer cell-specific cytotoxicity for multimodal tumor therapy. ACS Nano 14(11), 14919–14928 (2020). https://doi.org/10.1021/acsnano.0c04370
  16. S. Xiao, Y. Lu, M. Feng, M. Dong, Z. Cao et al., Multifunctional FeS2 theranostic nanops for photothermal-enhanced chemodynamic/photodynamic cancer therapy and photoacoustic imaging. Chem. Eng. J. 396, 125294 (2020). https://doi.org/10.1016/j.cej.2020.125294
  17. M. Liu, H. Zhu, Y. Wang, C. Sevencan, B.L. Li, Functionalized MoS2-based nanomaterials for cancer phototherapy and other biomedical applications. ACS Mater. Lett. 3(5), 462–496 (2021). https://doi.org/10.1021/acsmaterialslett.1c00073
  18. Y. Zhao, M. Song, X. Yang, J. Yang, C. Du et al., Amorphous Ag2-xCuxS quantum dots: “All-in-one” theranostic nanomedicines for near-infrared fluorescence/photoacoustics dual-modal-imaging-guided photothermal therapy. Chem. Eng. J. 399, 125777 (2020). https://doi.org/10.1016/j.cej.2020.125777
  19. G. Xu, X. Bao, J. Chen, B. Zhang, D. Li et al., In vivo tumor photoacoustic imaging and photothermal therapy based on supra-(carbon nanodots). Adv. Healthc. Mater. 8(2), e1800995 (2019). https://doi.org/10.1002/adhm.201800995
  20. C. Yang, M.R. Younis, J. Zhang, J. Qu, J. Lin et al., Programmable NIR-II photothermal-enhanced starvation-primed chemodynamic therapy using glucose oxidase-functionalized ancient pigment nanosheets. Small 16(25), e2001518 (2020). https://doi.org/10.1002/smll.202001518
  21. S.W. Jun, P. Manivasagan, J. Kwon, V.T. Nguyen, S. Mondal et al., Folic acid-conjugated chitosan-functionalized graphene oxide for highly efficient photoacoustic imaging-guided tumor-targeted photothermal therapy. Int. J. Biol. Macromol. 155, 961–971 (2020). https://doi.org/10.1016/j.ijbiomac.2019.11.055
  22. P. Sun, X. Jiang, B. Sun, H. Wang, J. Li et al., Electron-acceptor density adjustments for preparation conjugated polymers with NIR-II absorption and brighter NIR-II fluorescence and 1064 nm active photothermal/gas therapy. Biomaterials 280, 121319 (2022). https://doi.org/10.1016/j.biomaterials.2021.121319
  23. X. Wang, X. Wang, Q. Yue, H. Xu, X. Zhong et al., Liquid exfoliation of tin nanodots as novel sonosensitizers for photothermal-enhanced sonodynamic therapy against cancer. Nano Today 39, 101170 (2021). https://doi.org/10.1016/j.nantod.2021.101170
  24. S. Hao, H. Han, Z. Yang, M. Chen, Y. Jiang et al., Recent advancements on photothermal conversion and antibacterial applications over mxenes-based materials. Nano-Micro Lett. 14, 178 (2022). https://doi.org/10.1007/s40820-022-00901-w
  25. B. Guo, Z. Sheng, D. Hu, C. Liu, H. Zheng et al., Through scalp and skull NIR-II photothermal therapy of deep orthotopic brain tumors with precise photoacoustic imaging guidance. Adv. Mater. 30(35), e1802591 (2018). https://doi.org/10.1002/adma.201802591
  26. Y. Wan, G. Lu, W.C. Wei, Y.H. Huang, S.L. Li et al., Stable organic photosensitizer nanops with absorption peak beyond 800 nanometers and high reactive oxygen species yield for multimodality phototheranostics. ACS Nano 14(8), 9917–9928 (2020). https://doi.org/10.1021/acsnano.0c02767
  27. M. Li, Z. Li, D. Yu, M. Wang, D. Wang et al., Quinoid conjugated polymer nanops with NIR-II absorption peak toward efficient photothermal therapy. Chem. (2022). https://doi.org/10.1002/chem.202202930
  28. Y. Zou, W. Liu, W. Sun, J. Du, J. Fan et al., Highly inoxidizable heptamethine cyanine–glucose oxidase conjugate nanoagent for combination of enhanced photothermal therapy and tumor starvation. Adv. Funct. Mater. 32(17), 2111853 (2022). https://doi.org/10.1002/adfm.202111853
  29. J. Wu, Y. Zhang, K. Jiang, X. Wang, N.T. Blum et al., Enzyme-engineered conjugated polymer nanoplatform for activatable companion diagnostics and multistage augmented synergistic therapy. Adv. Mater. 34(18), e2200062 (2022). https://doi.org/10.1002/adma.202200062
  30. D. Zheng, P. Yu, Z. Wei, C. Zhong, M. Wu et al., RBC membrane camouflaged semiconducting polymer nanops for near-infrared photoacoustic imaging and photothermal therapy. Nano-Micro Lett. 12, 94 (2020). https://doi.org/10.1007/s40820-020-00429-x
  31. H. Zhou, D. Tang, X. Kang, H. Yuan, Y. Yu et al., Degradable pseudo conjugated polymer nanops with NIR-II photothermal effect and cationic quaternary phosphonium structural bacteriostasis for anti-infection therapy. Adv. Sci. 9(16), e2200732 (2022). https://doi.org/10.1002/advs.202200732
  32. S. Li, Q. Deng, Y. Zhang, X. Li, G. Wen et al., Rational design of conjugated small molecules for superior photothermal theranostics in the NIR-II biowindow. Adv. Mater. 32(33), e2001146 (2020). https://doi.org/10.1002/adma.202001146
  33. P. Chen, F. Qu, S. Chen, J. Li, Q. Shen et al., Bandgap modulation and lipid intercalation generates ultrabright D-A-D-based zwitterionic small-molecule nanoagent for precise NIR-II excitation phototheranostic applications. Adv. Funct. Mater. 32(52), 202208463 (2022). https://doi.org/10.1002/adfm.202208463
  34. C. Zhang, M. Xu, Z. Zeng, X. Wei, S. He et al., A polymeric extracellular matrix nanoremodeler for activatable cancer photo-immunotherapy. Angew. Chem. Int. Ed. 62(12), e202217339 (2023). https://doi.org/10.1002/anie.202217339
  35. D. Wang, J. Liu, C. Wang, W. Zhang, G. Yang et al., Microbial synthesis of prussian blue for potentiating checkpoint blockade immunotherapy. Nat. Commun. 14(1), 2943 (2023). https://doi.org/10.1038/s41467-023-38796-9
  36. Y. Qin, X. Chen, Y. Gui, H. Wang, B.Z. Tang et al., Self-assembled metallacage with second near-infrared aggregation-induced emission for enhanced multimodal theranostics. J. Am. Chem. Soc. 144(28), 12825–12833 (2022). https://doi.org/10.1021/jacs.2c03895
  37. P. Xiao, W. Xie, J. Zhang, Q. Wu, Z. Shen et al., De novo design of reversibly PH-switchable NIR-II aggregation-induced emission luminogens for efficient phototheranostics of patient-derived tumor xenografts. J. Am. Chem. Soc. 145(1), 334–344 (2023). https://doi.org/10.1021/jacs.2c10076
  38. D. Yan, M. Wang, Q. Wu, N. Niu, M. Li et al., Multimodal imaging-guided photothermal immunotherapy based on a versatile NIR-II aggregation-induced emission luminogen. Angew. Chem. Int. Ed. 61(27), e202202614 (2022). https://doi.org/10.1002/anie.202202614
  39. J. Li, J. Wang, J. Zhang, T. Han, X. Hu et al., A facile strategy of boosting photothermal conversion efficiency through state transformation for cancer therapy. Adv. Mater. 33(51), e2105999 (2021). https://doi.org/10.1002/adma.202105999
  40. R. Zheng, Q. Zhao, W. Qing, S. Li, Z. Liu et al., Carrier-free delivery of ultrasmall π-conjugated oligomer nanops with photothermal conversion over 80% for cancer theranostics. Small 18(4), e2104521 (2022). https://doi.org/10.1002/smll.202104521
  41. S. Chen, Y. Pan, K. Chen, P. Chen, Q. Shen et al., Increasing molecular planarity through donor/side-chain engineering for improved NIR-IIa fluorescence imaging and NIR-II photothermal therapy under 1064 nm. Angew. Chem. Int. Ed. 62(6), e202215372 (2023). https://doi.org/10.1002/anie.202215372
  42. X. Wu, Y. Jiang, N.J. Rommelfanger, F. Yang, Q. Zhou et al., Tether-free photothermal deep-brain stimulation in freely behaving mice via wide-field illumination in the Near-Infrared-II window. Nat. Biomed. Eng. 6(6), 754–770 (2022). https://doi.org/10.1038/s41551-022-00862-w
  43. C. Zhou, L. Zhang, T. Sun, Y. Zhang, Y. Liu et al., Activatable NIR-II plasmonic nanotheranostics for efficient photoacoustic imaging and photothermal cancer therapy. Adv. Mater. 33(3), 2006532 (2020). https://doi.org/10.1002/adma.202006532
  44. D. Tang, H. Zhou, M. Cui, G. Liang, H. Zhang et al., NIR-II light accelerated prodrug reduction of Pt(iv)-incorporating pseudo semiconducting polymers for robust degradation and maximized photothermal/chemo-immunotherapy. Adv. Mater. 35(28), 2300048 (2023). https://doi.org/10.1002/adma.202300048
  45. A. Abdurahman, T.J.H. Hele, Q. Gu, J. Zhang, Q. Peng et al., Understanding the luminescent nature of organic radicals for efficient doublet emitters and pure-red light-emitting diodes. Nat. Mater. 19(11), 1224–1229 (2020). https://doi.org/10.1038/s41563-020-0705-9
  46. H. Guo, Q. Peng, X.K. Chen, Q. Gu, S. Dong et al., High stability and luminescence efficiency in donor-acceptor neutral radicals not following the aufbau principle. Nat. Mater. 18(9), 977–984 (2019). https://doi.org/10.1038/s41563-019-0433-1
  47. X. Ai, E.W. Evans, S. Dong, A.J. Gillett, H. Guo et al., Efficient radical-based light-emitting diodes with doublet emission. Nature 563(7732), 536–540 (2018). https://doi.org/10.1038/s41586-018-0695-9
  48. K. Oyaizu, H. Nishide, Radical polymers for organic electronic devices: A radical departure from conjugated polymers? Adv. Mater. 21(22), 2339–2344 (2009). https://doi.org/10.1002/adma.200803554
  49. J. Kida, D. Aoki, H. Otsuka, Mechanophore activation enhanced by hydrogen bonding of diarylurea motifs: an efficient supramolecular force-transducing system. Aggregate. 2(3), e50 (2021). https://doi.org/10.1002/agt2.50
  50. T. Janoschka, M.D. Hager, U.S. Schubert, Powering up the future: Radical polymers for battery applications. Adv. Mater. 24(48), 6397–6409 (2012). https://doi.org/10.1002/adma.201203119
  51. W. Zeng, J. Wu, Open-shell graphene fragments. Chem 7(2), 358–386 (2021). https://doi.org/10.1016/j.chempr.2020.10.009
  52. M. Slota, A. Keerthi, W.K. Myers, E. Tretyakov, M. Baumgarten et al., Magnetic edge states and coherent manipulation of graphene nanoribbons. Nature 557(7707), 691–695 (2018). https://doi.org/10.1038/s41586-018-0154-7
  53. X. Hu, W. Wang, D. Wang, Y. Zheng, The electronic applications of stable diradicaloids: present and future. J. Mater. Chem. C 6(42), 11232–11242 (2018). https://doi.org/10.1039/c8tc04484h
  54. L. Li, Y. Li, A study on the origin of the radical in fullerene and graphene. The J. Phys. Chem. C 122(16), 8780–8787 (2018). https://doi.org/10.1021/acs.jpcc.8b00515
  55. Y. Li, L. Li, Y. Wu, Y. Li, A review on the origin of synthetic metal radical: Singlet open-shell radical ground state? J. Phys. Chem. C 121(15), 8579–8588 (2017). https://doi.org/10.1021/acs.jpcc.6b12936
  56. J. Guo, C. Zhou, S. Xie, S. Luo, T.Y. Gopalakrishna et al., Large aromatic hydrocarbon radical cation with global aromaticity and state-associated magnetic activity. Chem. Mater. 32(14), 5927–5936 (2020). https://doi.org/10.1021/acs.chemmater.9b05099
  57. Z. Chen, W. Li, M.A. Sabuj, Y. Li, W. Zhu et al., Evolution of the electronic structure in open-shell donor-acceptor organic semiconductors. Nat. Commun. 12(1), 5889 (2021). https://doi.org/10.1038/s41467-021-26173-3
  58. T. Luo, Y. Wang, J. Hao, P.A. Chen, Y. Hu et al., Furan-extended helical rylenes with fjord edge topology and tunable optoelectronic properties. Angew. Chem. Int. Ed. 62(5), e202214653 (2023). https://doi.org/10.1002/anie.202214653
  59. Z. Chen, W. Li, Y. Zhang, Z. Wang, W. Zhu et al., Aggregation-induced radical of donor-acceptor organic semiconductors. J. Phys. Chem. Lett. 12(40), 9783–9790 (2021). https://doi.org/10.1021/acs.jpclett.1c02463
  60. B. Tang, W.L. Li, Y. Chang, B. Yuan, Y. Wu et al., A supramolecular radical dimer: High-efficiency NIR-II photothermal conversion and therapy. Angew. Chem. Int. Ed. 58(43), 15526–15531 (2019). https://doi.org/10.1002/anie.201910257
  61. B. Lu, Y. Chen, P. Li, B. Wang, K. Mullen et al., Stable radical anions generated from a porous perylenediimide metal-organic framework for boosting near-infrared photothermal conversion. Nat. Commun. 10(1), 767 (2019). https://doi.org/10.1038/s41467-019-08434-4
  62. Z. Mi, P. Yang, R. Wang, J. Unruangsri, W. Yang et al., Stable radical cation-containing covalent organic frameworks exhibiting remarkable structure-enhanced photothermal conversion. J. Am. Chem. Soc. 141(36), 14433–14442 (2019). https://doi.org/10.1021/jacs.9b07695
  63. G. Chen, J. Sun, Q. Peng, Q. Sun, G. Wang et al., Biradical-featured stable organic-small-molecule photothermal materials for highly efficient solar-driven water evaporation. Adv. Mater. 32(29), e1908537 (2020). https://doi.org/10.1002/adma.201908537
  64. X. Cui, G. Lu, S. Dong, S. Li, Y. Xiao et al., Stable π-radical nanops as versatile photosensitizers for effective hypoxia-overcoming photodynamic therapy. Mater. Horiz. 8(2), 571–576 (2021). https://doi.org/10.1039/d0mh01312a
  65. X. Cui, Z. Zhang, Y. Yang, S. Li, C.-S. Lee, Organic radical materials in biomedical applications: state of the art and perspectives. Exploration 2(2), 20210264 (2022). https://doi.org/10.1002/exp.20210264
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