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Vol. 12 (2020)

Molecular Design of Conjugated Small Molecule Nanoparticles for Synergistically Enhanced PTT/ PDT

https://doi.org/10.1007/s40820-020-00474-6
Wei Shao
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China
Chuang Yang
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China
Fangyuan Li
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China
Jiahe Wu
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China
Nan Wang
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China
Qiang Ding
Jiangsu Breast Disease Center, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu, People’s Republic of China
Jianqing Gao
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China
Daishun Ling
Institute of Pharmaceutics and Hangzhou Institute of Innovative Medicine, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, Zhejiang, People’s Republic of China

Corresponding Author: Fangyuan Li

lfy@zju.edu.cn

Nano-Micro Letters, Vol. 12 (2020), Article Number: 147

Abstract

Simultaneous photothermal therapy (PTT) and photodynamic therapy (PDT) is beneficial for enhanced cancer therapy due to the synergistic effect. Conventional materials developed for synergistic PTT/PDT are generally multicomponent agents that need complicated preparation procedures and be activated by multiple laser sources. The emerging monocomponent diketopyrrolopyrrole (DPP)-based conjugated small molecular agents enable dual PTT/PDT under a single laser irradiation, but suffer from low singlet oxygen quantum yield, which severely restricts the therapeutic efficacy. Herein, we report acceptor-oriented molecular design of a donor–acceptor–donor (D–A–D) conjugated small molecule (IID-ThTPA)-based phototheranostic agent, with isoindigo (IID) as selective acceptor and triphenylamine (TPA) as donor. The strong D–A strength and narrow singlet–triplet energy gap endow IID-ThTPA nanoparticles (IID-ThTPA NPs) high mass extinction coefficient (18.2 L g−1 cm−1), competitive photothermal conversion efficiency (35.4%), and a dramatically enhanced singlet oxygen quantum yield (84.0%) comparing with previously reported monocomponent PTT/PDT agents. Such a high PTT/PDT performance of IID-ThTPA NPs achieved superior tumor cooperative eradicating capability in vitro and in vivo.


Highlights:


1 A donor–acceptor–donor (D–A–D) conjugated small molecule IID-ThTPA with narrow singlet–triplet energy gap is synthesized via acceptor-oriented molecular design.
2 IID-ThTPA nanoparticles exhibit not only competitive photothermal conversion efficiency (35.4%), but also a dramatically high singlet oxygen quantum yield (84.0%).
3 IID-ThTPA nanoparticles enable superior cooperative tumor PTT/PDT eradicating capability both in vitro and in vivo.

Keywords

Molecular design Isoindigo Conjugated small molecule nanoparticles Singlet–triplet energy gap Synergistic PTT/PDT
Shao, Wei, Chuang Yang, Fangyuan Li, Jiahe Wu, Nan Wang, Qiang Ding, Jianqing Gao, and Daishun Ling. 2020. “Molecular Design of Conjugated Small Molecule Nanoparticles for Synergistically Enhanced PTT/ PDT”. Nano-Micro Letters 12 (July):147. https://doi.org/10.1007/s40820-020-00474-6.
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References
  1. M. Ferrari, Cancer nanotechnology: opportunities and challenges. Nat. Rev. Cancer 5, 161–171 (2005). https://doi.org/10.1038/nrc1566
  2. Y. Cai, W. Si, W. Huang, P. Chen, J. Shao, X. Dong, Organic dye based nanoparticles for cancer phototheranostics. Small 14, 1704247 (2018). https://doi.org/10.1002/smll.201704247
  3. L. Cheng, C. Wang, L. Feng, K. Yang, Z. Liu, Functional nanomaterials for phototherapies of cancer. Chem. Rev. 114, 10869–10939 (2014). https://doi.org/10.1021/cr400532z
  4. S. Gai, G. Yang, P. Yang, F. He, J. Lin, D. Jin, B. Xing, Recent advances in functional nanomaterials for light–triggered cancer therapy. Nano Today 19, 146–187 (2018). https://doi.org/10.1016/j.nantod.2018.02.010
  5. D. Peer, J.M. Karp, S. Hong, O.C. Farokhzad, R. Margalit, R. Langer, Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2, 751–760 (2007). https://doi.org/10.1038/nnano.2007.387
  6. Z. Meng, W. Hou, H. Zhou, L. Zhou, H. Chen, C. Wu, Therapeutic considerations and conjugated polymer-based photosensitizers for photodynamic therapy. Macromol. Rapid Commun. 39, 1700614 (2018). https://doi.org/10.1002/marc.201700614
  7. B. Tian, C. Wang, S. Zhang, L. Feng, Z. Liu, Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide. ACS Nano 5, 7000–7009 (2011). https://doi.org/10.1021/nn201560b
  8. M.R. Younis, C. Wang, R. An, S. Wang, M.A. Younis et al., Low power single laser activated synergistic cancer phototherapy using photosensitizer functionalized dual plasmonic photothermal nanoagents. ACS Nano 13, 2544–2557 (2019). https://doi.org/10.1021/acsnano.8b09552
  9. M. Guo, H. Mao, Y. Li, A. Zhu, H. He et al., Dual imaging-guided photothermal/photodynamic therapy using micelles. Biomaterials 35, 4656–4666 (2014). https://doi.org/10.1016/j.biomaterials.2014.02.018
  10. L. Li, Y. Liu, P. Hao, Z. Wang, L. Fu, Z. Ma, J. Zhou, PEDOT nanocomposites mediated dual-modal photodynamic and photothermal targeted sterilization in both NIR I and II window. Biomaterials 41, 132–140 (2015). https://doi.org/10.1016/j.biomaterials.2014.10.075
  11. Y. Cao, H. Dong, Z. Yang, X. Zhong, Y. Chen, W. Dai, X. Zhang, Aptamer-conjugated graphene quantum dots/porphyrin derivative theranostic agent for intracellular cancer-related microrna detection and fluorescence-guided photothermal/photodynamic synergetic therapy. ACS Appl. Mater. Interfaces 9, 159–166 (2017). https://doi.org/10.1021/acsami.6b13150
  12. H.S. Han, K.Y. Choi, H. Lee, M. Lee, J.Y. An et al., Gold-nanoclustered hyaluronan nano-assemblies for photothermally maneuvered photodynamic tumor ablation. ACS Nano 10, 10858–10868 (2016). https://doi.org/10.1021/acsnano.6b05113
  13. Q. Jia, J. Ge, W. Liu, S. Liu, G. Niu, L. Guo, H. Zhang, P. Wang, Gold nanorod@silica-carbon dots as multifunctional phototheranostics for fluorescence and photoacoustic imaging-guided synergistic photodynamic/photothermal therapy. Nanoscale 8, 13067–13077 (2016). https://doi.org/10.1039/c6nr03459d
  14. Y.K. Kim, H.K. Na, S. Kim, H. Jang, S.J. Chang, D.H. Min, One-pot synthesis of multifunctional Au@graphene oxide nanocolloid core@shell nanoparticles for Raman bioimaging, photothermal, and photodynamic therapy. Small 11, 2527–2535 (2015). https://doi.org/10.1002/smll.201402269
  15. L. Dou, Y. Liu, Z. Hong, G. Li, Y. Yang, Low-bandgap near-IR conjugated polymers/molecules for organic electronics. Chem. Rev. 115, 12633–12665 (2015). https://doi.org/10.1021/acs.chemrev.5b00165
  16. Z. Liu, G. Zhang, D. Zhang, Modification of side chains of conjugated molecules and polymers for charge mobility enhancement and sensing functionality. Acc. Chem. Res. 51, 1422–1432 (2018). https://doi.org/10.1021/acs.accounts.8b00069
  17. A.L. Antaris, H. Chen, K. Cheng, Y. Sun, G. Hong et al., A small-molecule dye for NIR-II imaging. Nat. Mater. 15, 235–242 (2016). https://doi.org/10.1038/nmat4476
  18. Q. Yang, Z. Hu, S. Zhu, R. Ma, H. Ma et al., Donor engineering for NIR-II molecular fluorophores with enhanced fluorescent performance. J. Am. Chem. Soc. 140, 1715–1724 (2018). https://doi.org/10.1021/jacs.7b10334
  19. Q. Yang, Z. Ma, H. Wang, B. Zhou, S. Zhu et al., Rational design of molecular fluorophores for biological imaging in the NIR-II window. Adv. Mater. 29, 1605497 (2017). https://doi.org/10.1002/adma.201605497
  20. M. Gsänger, D. Bialas, L. Huang, M. Stolte, F. Würthner, Organic semiconductors based on dyes and color pigments. Adv. Mater. 28, 3615–3645 (2016). https://doi.org/10.1002/adma.201505440
  21. Y. Cai, P. Liang, W. Si, B. Zhao, J. Shao et al., A selenophene substituted diketopyrrolopyrrole nanotheranostic agent for highly efficient photoacoustic/infrared-thermal imaging-guided phototherapy. Org. Chem. Front. 5, 98–105 (2018). https://doi.org/10.1039/c7qo00755h
  22. Y. Cai, P. Liang, Q. Tang, X. Yang, W. Si, W. Huang, Q. Zhang, X. Dong, Diketopyrrolopyrrole-triphenylamine organic nanoparticles as multifunctional reagents for photoacoustic imaging-guided photodynamic/photothermal synergistic tumor therapy. ACS Nano 11, 1054–1063 (2017). https://doi.org/10.1021/acsnano.6b07927
  23. P. Liang, Y. Wang, P. Wang, J. Zou, H. Xu, Y. Zhang, W. Si, X. Dong, Triphenylamine flanked furan-diketopyrrolopyrrole for multi-imaging guided photothermal/photodynamic cancer therapy. Nanoscale 9, 18890–18896 (2017). https://doi.org/10.1039/c7nr07204j
  24. Y. Lyu, J. Zeng, Y. Jiang, X. Zhen, T. Wang, S. Qiu, X. Lou, M. Gao, K. Pu, Enhancing both biodegradability and efficacy of semiconducting polymer nanoparticles for photoacoustic imaging and photothermal therapy. ACS Nano 12, 1801–1810 (2018). https://doi.org/10.1021/acsnano.7b08616
  25. J. Shen, J. Chen, Z. Ke, D. Zou, L. Sun, J. Zou, Heavy atom-free semiconducting polymer with high singlet oxygen quantum yield for prostate cancer synergistic phototherapy. Mater. Chem. Front. 3, 1123–1127 (2019). https://doi.org/10.1039/c9qm00158a
  26. Q. Wang, Y. Dai, J. Xu, J. Cai, X. Niu, L. Zhang, R. Chen, Q. Shen, W. Huang, Q. Fan, All-in-one phototheranostics: single laser triggers NIR-II fluorescence/photoacoustic imaging guided photothermal/photodynamic/chemo combination therapy. Adv. Funct. Mater. 29, 1901480 (2019). https://doi.org/10.1002/adfm.201901480
  27. J. Zou, L. Xue, N. Yang, Y. Ren, Z. Fan et al., A glutathione responsive pyrrolopyrrolidone nanotheranostic agent for turn-on fluorescence imaging guided photothermal/photodynamic cancer therapy. Mater. Chem. Front. 3, 2143–2150 (2019). https://doi.org/10.1039/c9qm00471h
  28. J. Zou, J. Zhu, Z. Yang, L. Li, W. Fan et al., A photo theranostic strategy to continuously deliver singlet oxygen in the dark and hypoxic tumor microenvironment. Angew. Chem. Int. Ed. 59, 8833–8838 (2020). https://doi.org/10.1002/anie.201914384
  29. K. Lu, C. He, W. Lin, Nanoscale metal-organic framework for highly effective photodynamic therapy of resistant head and neck cancer. J. Am. Chem. Soc. 136, 16712–16715 (2014). https://doi.org/10.1021/ja508679h
  30. X. Miao, W. Hu, T. He, H. Tao, Q. Wang et al., Deciphering the intersystem crossing in near-infrared bodipy photosensitizers for highly efficient photodynamic therapy. Chem. Sci. 10, 3096–3102 (2019). https://doi.org/10.1039/c8sc04840a
  31. M. Schulze, A. Steffen, F. Wurthner, Near-IR phosphorescent ruthenium(ii) and iridium(iii) perylene bisimide metal complexes. Angew. Chem. Int. Ed. 54, 1570–1573 (2015). https://doi.org/10.1002/anie.201410437
  32. K. Wen, X. Xu, J. Chen, L. Lv, L. Wu et al., Triplet tellurophene-based semiconducting polymer nanoparticles for near-infrared-mediated cancer theranostics. ACS Appl. Mater. Interfaces 11, 17884–17893 (2019). https://doi.org/10.1021/acsami.9b05196
  33. T. Yogo, Y. Urano, Y. Ishitsuka, F. Maniwa, T. Nagano, Highly efficient and photostable photosensitizer based on bodipy chromophore. J. Am. Chem. Soc. 127, 12162–12163 (2005). https://doi.org/10.1021/ja0528533
  34. J. Zou, Z. Yin, P. Wang, D. Chen, J. Shao, Q. Zhang, L. Sun, W. Huang, X. Dong, Photosensitizer synergistic effects: D–A–D structured organic molecule with enhanced fluorescence and singlet oxygen quantum yield for photodynamic therapy. Chem. Sci. 9, 2188–2194 (2018). https://doi.org/10.1039/c7sc04694d
  35. Y. Cakmak, S. Kolemen, S. Duman, Y. Dede, Y. Dolen et al., Designing excited states: theory-guided access to efficient photosensitizers for photodynamic action. Angew. Chem. Int. Ed. 50, 11937–11941 (2011). https://doi.org/10.1002/anie.201105736
  36. S. Kolemen, M. Isik, G.M. Kim, D. Kim, H. Geng et al., Intracellular modulation of excited-state dynamics in a chromophore dyad: differential enhancement of photocytotoxicity targeting cancer cells. Angew. Chem. Int. Ed. 54, 5340–5344 (2015). https://doi.org/10.1002/anie.201411962
  37. S.H. Lim, C. Thivierge, P. Nowak-Sliwinska, J. Han, H. van den Bergh, G. Wagnieres, K. Burgess, H.B. Lee, In vitro and in vivo photocytotoxicity of boron dipyrromethene derivatives for photodynamic therapy. J. Med. Chem. 53, 2865–2874 (2010). https://doi.org/10.1021/jm901823u
  38. V.N. Nguyen, S. Qi, S. Kim, N. Kwon, G. Kim, Y. Yim, S. Park, J. Yoon, An emerging molecular design approach to heavy-atom-free photosensitizers for enhanced photodynamic therapy under hypoxia. J. Am. Chem. Soc. 141, 16243–16248 (2019). https://doi.org/10.1021/jacs.9b09220
  39. T. Lei, J.Y. Wang, J. Pei, Design, synthesis, and structure-property relationships of isoindigo-based conjugated polymers. Acc. Chem. Res. 47, 1117–1126 (2014). https://doi.org/10.1021/ar400254j
  40. R. Stalder, J. Mei, K.R. Graham, L.A. Estrada, J.R. Reynolds, Isoindigo, a versatile electron-deficient unit for high-performance organic electronics. Chem. Mater. 26, 664–678 (2013). https://doi.org/10.1021/cm402219v
  41. J. Yang, Z. Zhao, H. Geng, C. Cheng, J. Chen et al., Isoindigo-based polymers with small effective masses for high-mobility ambipolar field-effect transistors. Adv. Mater. 29, 1702115 (2017). https://doi.org/10.1002/adma.201702115
  42. L. Zhu, M. Wang, B. Li, C. Jiang, Q. Li, High efficiency organic photovoltaic devices based on isoindigo conjugated polymers with a thieno[3,2-b]thiophene π-bridge. J. Mater. Chem. A 4, 16064–16072 (2016). https://doi.org/10.1039/c6ta07138d
  43. R. Ngoune, A. Peters, D. von Elverfeldt, K. Winkler, G. Pütz, Accumulating nanoparticles by EPR: a route of no return. J. Controlled Release 238, 58–70 (2016). https://doi.org/10.1016/j.jconrel.2016.07.028
  44. D.K. Roper, W. Ahn, M. Hoepfner, Microscale heat transfer transduced by surface plasmon resonant gold nanoparticles. J. Phys. Chem. C 111, 3636–3641 (2007). https://doi.org/10.1021/jp064341w
  45. L. Guo, G. Niu, X. Zheng, J. Ge, W. Liu, Q. Jia, P. Zhang, H. Zhang, P. Wang, Single near-infrared emissive polymer nanoparticles as versatile phototheranostics. Adv. Sci. 4, 1700085 (2017). https://doi.org/10.1002/advs.201700085
  46. P. Sun, X. Wang, G. Wang, W. Deng, Q. Shen, R. Jiang, W. Wang, Q. Fan, W. Huang, A perylene diimide zwitterionic polymer for photoacoustic imaging guided photothermal/photodynamic synergistic therapy with single near-infrared irradiation. J. Mater. Chem. B 6, 3395–3403 (2018). https://doi.org/10.1039/c8tb00845k
  47. Q. Wang, B. Xia, J. Xu, X. Niu, J. Cai, Q. Shen, W. Wang, W. Huang, Q. Fan, Biocompatible small organic molecule phototheranostics for NIR-II fluorescence/photoacoustic imaging and simultaneous photodynamic/photothermal combination therapy. Mater. Chem. Front. 3, 650–655 (2019). https://doi.org/10.1039/c9qm00036d
  48. Q. Wang, J. Xu, R. Geng, J. Cai, J. Li, C. Xie, W. Tang, Q. Shen, W. Huang, Q. Fan, High performance one-for-all phototheranostics: NIR-II fluorescence imaging guided mitochondria-targeting phototherapy with a single-dose injection and 808 nm laser irradiation. Biomaterials 231, 119671 (2020). https://doi.org/10.1016/j.biomaterials.2019.119671
  49. X. Yang, Q. Yu, N. Yang, L. Xue, J. Shao, B. Li, J. Shao, X. Dong, Thieno[3,2-b]thiophene-DPP based near-infrared nanotheranostic agent for dual imaging-guided photothermal/photodynamic synergistic therapy. J. Mater. Chem. B 7, 2454–2462 (2019). https://doi.org/10.1039/c8tb03185a
  50. S. Ye, J. Rao, S. Qiu, J. Zhao, H. He et al., Rational design of conjugated photosensitizers with controllable photoconversion for dually cooperative phototherapy. Adv. Mater. 30, 1801216 (2018). https://doi.org/10.1002/adma.201801216
  51. J. Zhu, J. Zou, Z. Zhang, J. Zhang, Y. Sun, X. Dong, Q. Zhang, An NIR triphenylamine grafted BODIPY derivative with high photothermal conversion efficiency and singlet oxygen generation for imaging guided phototherapy. Mater. Chem. Front. 3, 1523–1531 (2019). https://doi.org/10.1039/c9qm00044e
  52. J. Chen, K. Wen, H. Chen, S. Jiang, X. Wu, L. Lv, A. Peng, S. Zhang, H. Huang, Achieving high-performance photothermal and photodynamic effects upon combining D–A structure and nonplanar conformation. Small 16, 2000909 (2020). https://doi.org/10.1002/smll.202000909
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