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Vol. 13 (2021)

Targeting Hypoxic Tumors with Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy

https://doi.org/10.1007/s40820-021-00616-4
Di Gao
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Ting Chen
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Shuojia Chen
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Xuechun Ren
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Yulong Han
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA 02138, USA
Yiwei Li
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA 02138, USA
Ying Wang
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Xiaoqing Guo
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Hao Wang
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Xing Chen
School of Public Health, Guangxi Medical University, Nanning 530000, People’s Republic of China
Ming Guo
School of Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Yu Shrike Zhang
Division of Engineering in Medicine, Department of Medicine, Brigham and Womens Hospital, Harvard Medical School, Cambridge, MA 02139, USA
Guosong Hong
Department of Materials Science and Engineering, Stanford University, Stanford, CA 94305, USA
Xingcai Zhang
Paulson School of Engineering and Applied Sciences, John A, Harvard University, Cambridge, MA 02138, USA
Zhongmin Tian
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China
Zhe Yang
The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, People’s Republic of China

Corresponding Author: Zhe Yang

yangzhe@xjtu.edu.cn

Nano-Micro Letters, Vol. 13 (2021), Article Number: 99

Abstract

Hypoxia is a feature of solid tumors and it hinders the therapeutic efficacy of oxygen-dependent cancer treatment. Herein, we have developed all-organic oxygen-independent hybrid nanobullets ZPA@HA-ACVA-AZ for the “precise strike” of hypoxic tumors through the dual-targeting effects from surface-modified hyaluronic acid (HA) and hypoxia-dependent factor carbonic anhydrase IX (CA IX)-inhibitor acetazolamide (AZ). The core of nanobullets is the special zinc (II) phthalocyanine aggregates (ZPA) which could heat the tumor tissues upon 808-nm laser irradiation for photothermal therapy (PTT), along with the alkyl chain-functionalized thermally decomposable radical initiator ACVA-HDA on the side chain of HA for providing oxygen-independent alkyl radicals for ablating hypoxic cancer cells by thermodynamic therapy (TDT). The results provide important evidence that the combination of reverse hypoxia hallmarks CA IX as targets for inhibition by AZ and synergistic PTT/TDT possess incomparable therapeutic advantages over traditional (reactive oxygen species (ROS)-mediated) cancer treatment for suppressing the growth of both hypoxic tumors and their metastasis.


Highlights:


1 An all-organic hybrid nanobullets labeled as ZPA@HA-ACVA-AZ NBs was developed for the “precise strike”of hypoxic tumors through an oxygen-independently synergistic PTT/TDT, possessing therapeutic advantages over traditional ROS-mediated cancer treatment.
2 By feat of dual-targeting effect from surface-modified HA (targeting CD44 receptors) and AZ (targeting CA IX), the nanobullets accumulated at hypoxic tumors efficiently.
3 The synergism of intelligent nanobullets could suppress the primary breast tumor growth and lung metastasis via CA IX inhibition by AZ and synergistic PTT/TDT.

Keywords

Photothermal therapy (PTT) Thermodynamic therapy (TDT) Targeting hybrid nanobullet Hypoxia tumor Zinc phthalocyanine aggregate (ZPA)
Gao, Di, Ting Chen, Shuojia Chen, Xuechun Ren, Yulong Han, Yiwei Li, Ying Wang, Xiaoqing Guo, Hao Wang, Xing Chen, Ming Guo, Yu Shrike Zhang, Guosong Hong, Xingcai Zhang, Zhongmin Tian, and Zhe Yang. 2021. “Targeting Hypoxic Tumors With Hybrid Nanobullets for Oxygen-Independent Synergistic Photothermal and Thermodynamic Therapy”. Nano-Micro Letters 13 (March):99. https://doi.org/10.1007/s40820-021-00616-4.
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References
  1. J. Ouyang, X. Ji, X. Zhang, C. Feng, Z. Tang et al., In situ sprayed NIR-responsive, analgesic black phosphorus-based gel for diabetic ulcer treatment. Proc. Natl. Acad. Sci. USA 117(46), 28667–28677 (2020). https://doi.org/10.1073/pnas.2016268117
  2. Z. Yang, D. Gao, X.Q. Guo, L. Jin, J. Zheng et al., Fighting immune cold and reprogramming immunosuppressive tumor microenvironment with red blood cell membrane-camouflaged nanobullets. ACS Nano 12, 17442–17457 (2020). https://doi.org/10.1021/acsnano.0c07721
  3. D. Gao, P.C. Lo, Polymeric Micelles Encapsulating pH-responsive doxorubicin prodrug and glutathione-activated zinc (ii) phthalocyanine for combined chemotherapy and photodynamic therapy. J Control. Release 282, 46–61 (2018). https://doi.org/10.1016/j.jconrel.2018.04.030
  4. Z. Yang, R. Cheng, C.Y. Zhao, N. Sun, H.Y. Luo, Y. Chen et al., Thermo- and pH-dual responsive polymeric micelles with upper critical solution temperature behavior for photoacoustic imaging-guided synergistic chemo-photothermal therapy against subcutaneous and metastatic breast tumors. Theranostics 8, 4097–4115 (2018). https://doi.org/10.7150/thno.26195
  5. Q. Wu, G. Chen, K. Gong, J. Wang, X. Ge et al., MnO2-laden black phosphorus for MRI-guided synergistic PDT, PTT, and chemotherapy. Matter 1(2), 496–512 (2019). https://doi.org/10.1016/j.matt.2019.03.007
  6. D. Gao, X.Q. Guo, X.C. Zhang, S.J. Chen, Y. Wang et al., Multifunctional phototheranostic nanomedicine for cancer imaging and treatment. Mater. Today Bio. 5, 100035 (2019). https://doi.org/10.1016/j.mtbio.2019.100035
  7. X. Zhang, G. Parekh, B. Guo, X. Huang, Y. Dong et al., Polyphenol and self-assembly: metal polyphenol nanonetwork for drug delivery and pharmaceutical applications. Future Drug Discov. 1(1), FDD7 (2019). https://doi.org/10.4155/fdd-2019-0001
  8. Z. Tang, X. Zhang, Y. Shu, M. Guo, H. Zhang et al., Insights from nanotechnology in COVID-19 treatment. Nano Today 36, 101019 (2020). https://doi.org/10.1016/j.nantod.2020.101019
  9. M. Li, J. Xia, R. Tian, J. Wang, J. Fan et al., Near-infrared light-initiated molecular superoxide radical generator: rejuvenating photodynamic therapy against hypoxic tumors. J. Am. Chem. Soc. 140(44), 14851–14859 (2018). https://doi.org/10.1021/jacs.8b08658
  10. G. Lan, K. Ni, Z. Xu, S.S. Veroneau, Y. Song et al., Nanoscale metal–organic framework overcomes hypoxia for photodynamic therapy primed cancer immunotherapy. J. Am. Chem. Soc. 140(17), 5670–5673 (2018). https://doi.org/10.1021/jacs.8b01072
  11. X. Li, N. Kwon, T. Guo, Z. Liu, J. Yoon, Innovative strategies for hypoxic-tumor photodynamic therapy. Angew. Chem. Int. Ed. 57(36), 11522–11531 (2018). https://doi.org/10.1002/anie.201805138
  12. X. Zhang, Tea and cancer prevention. J. Cancer Res. Updates 4(2), 65–73 (2015). https://doi.org/10.6000/1929-2279.2015.04.02.4
  13. X.Q. Wang, F. Gao, X.Z. Zhang, Initiator-loaded gold nanocages as a light-induced free-radical generator for cancer therapy. Angew. Chem. Int. Ed. 56, 9029–9033 (2017). https://doi.org/10.1002/anie.201703159
  14. M.F. Wang, Y.J. Zhao, M.Y. Chang, B.B. Ding, J. Lin, Azo initiator loaded black mesoporous titania with multiple optical energy conversion for synergetic photo-thermal-dynamic therapy. ACS Appl. Mater. Interfaces 11, 47730–47738 (2019). https://doi.org/10.1021/acsami.9b17375
  15. J. Yang, R. Xie, L.L. Feng, B. Liu, J. Lin, Hyperthermia and controllable free radicals co-enhanced synergistic therapy in hypoxia enabled by near-infrared-ii light irradiation. ACS Nano 13, 13144–13160 (2019). https://doi.org/10.1021/acsnano.9b05985
  16. H. Xiang, H. Lin, L. Yu, Y. Chen, Hypoxia-irrelevant photonic thermodynamic cancer nanomedicine. ACS Nano 13, 2223–2235 (2019). https://doi.org/10.1021/acsnano.8b08910
  17. Y. Wan, G. Lu, J. Zhang, Z. Wang, X. Li et al., A biocompatible free radical nanogenerator with real-time monitoring capability for high performance sequential hypoxic tumor therapy. Adv. Funct. Mater. 29(39), 1903436 (2019). https://doi.org/10.1002/adfm.201903436
  18. H.S. Jung, J. Han, H. Shi, S. Koo, H. Singh et al., Overcoming the limits of hypoxia in photodynamic therapy: a carbonic anhydrase IX-targeted approach. J. Am. Chem. Soc. 139(22), 7595–7602 (2017). https://doi.org/10.1021/jacs.7b02396
  19. L. Meng, Y. Cheng, X. Tong, S. Gan, Y. Ding et al., Tumor oxygenation and hypoxia inducible factor-1 functional inhibition via a reactive oxygen species responsive nanoplatform for enhancing radiation therapy and abscopal effects. ACS Nano 12(8), 8308–8322 (2018). https://doi.org/10.1021/acsnano.8b03590
  20. D. Chiu, A. Tse, I. Xu, D. Cui, R. Lai et al., Hypoxia inducible factor HIF-1 promotes myeloid-derived suppressor cells accumulation through ENTPD2/CD39L1 in hepatocellular carcinoma. Nat. Commun. 8(1), 1–12 (2017). https://doi.org/10.1038/s41467-017-00530-7
  21. S. Pastorekova, R.J. Gillies, The role of carbonic anhydrase IX in cancer development: links to hypoxia, acidosis, and beyond. Cancer Metastasis Rev. 38(1), 65–77 (2019). https://doi.org/10.1007/s10555-019-09799-0
  22. C.T. Supuran, Carbonic anhydrases: novel therapeutic applications for inhibitors and activators. Nat. Rev. Drug Discov. 7(2), 168–181 (2008). https://doi.org/10.1038/nrd2467
  23. A. Angeli, M. Ferraroni, A. Nocentini, S. Selleri, P. Gratteri et al., Polypharmacology of epacadostat: a potent and selective inhibitor of the tumor associated carbonic anhydrases IX and XII. Chem. Comm. 55, 5720–5723 (2019). https://doi.org/10.1039/C8CC09568J
  24. C. Lomelino, R. McKenna, Carbonic anhydrase inhibitors: a review on the progress of patent literature (2011–2016). Expert Opin. Ther. Pat. 26(8), 947–956 (2016). https://doi.org/10.1080/13543776.2016.1203904
  25. C.T. Supuran, J.-Y. Winum, Carbonic anhydrase IX inhibitors in cancer therapy: an update. Future Med. Chem. 7(11), 1407–1414 (2015). https://doi.org/10.4155/fmc.15.71
  26. F. Ratto, E. Witort, F. Tatini, S. Centi, L. Lazzeri et al., Plasmonic particles that hit hypoxic cells. Adv. Funct. Mater. 25(2), 316–323 (2015). https://doi.org/10.1002/adfm.201402118
  27. Y. Jiang, J. Li, Z. Zeng, C. Xie, Y. Lyu et al., Organic photodynamic nanoinhibitor for synergistic cancer therapy. Angew. Chem. Int. Ed. 58(24), 8161–8165 (2019). https://doi.org/10.1002/anie.201903968
  28. W. Zhu, Y. Liu, Z. Yang, L. Zhang, L. Xiao et al., Albumin/sulfonamide stabilized iron porphyrin metal organic framework nanocomposites: targeting tumor hypoxia by carbonic anhydrase IX inhibition and T1–T2 dual mode MRI guided photodynamic/photothermal therapy. J Mater. Chem. B 6(2), 265–276 (2018). https://doi.org/10.1039/c7tb02818k
  29. M. Zhou, X. Zhang, J. Xie, R. Qi, H. Lu et al., pH-sensitive poly(β-amino ester)s nanocarriers facilitate the inhibition of drug resistance in breast cancer cells. Nanomaterials 8(11), 952–968 (2018). https://doi.org/10.3390/nano8110952
  30. J. Li, B.E.F. de Ávila, W. Gao, L. Zhang, J. Wang, Micro/nanorobots for biomedicine: Delivery, surgery, sensing, and detoxification. Sci. Robot 2(4), eaam6431 (2017). https://doi.org/10.1126/scirobotics.aam6431
  31. V. Vergaro, F. Scarlino, C. Bellomo, R. Rinaldi, D. Vergara et al., Drug-loaded polyelectrolyte microcapsules for sustained targeting of cancer cells. Adv. Drug Deliv. Rev. 63(9), 847–864 (2011). https://doi.org/10.1016/j.addr.2011.05.007
  32. Y. Niu, F.J. Stadler, T. He, X. Zhang, Y. Yu et al., Smart multifunctional polyurethane microcapsules for the quick release of anticancer drugs in BGC 823 and HeLa tumor cells. J. Mater. Chem. B 5(48), 9477–9481 (2017). https://doi.org/10.1039/c7tb02570j
  33. G. Parekh, Y.Y. Shi, J. Zheng, X. Zhang, S. Leporatti, Nano-carriers for targeted delivery and biomedical imaging enhancement. Ther. Deliv. 9, 451–468 (2018). https://doi.org/10.4155/tde-2018-0013
  34. Y. Yang, P. Jin, X. Zhang, N. Ravichandran, H. Ying et al., New epigallocatechin gallate (EGCG) nanocomplexes co-assembled with 3-mercapto-1-hexanol and β-lactoglobulin for improvement of antitumor activity. J. Biomed. Nanotechnol. 13(7), 805–814 (2017). https://doi.org/10.1166/jbn.2017.2400
  35. Z. Tang, N. Kong, X. Zhang, Y. Liu, P. Hu et al., A materials-science perspective on tackling COVID-19. Nat. Rev. Mater. 5(11), 847–860 (2020). https://doi.org/10.1038/s41578-020-00247-y
  36. D. Vergara, C. Bellomo, X. Zhang, V. Vergaro, A. Tinelli et al., Lapatinib/Paclitaxel polyelectrolyte nanocapsules for overcoming multidrug resistance in ovarian cancer. Nanomedicine 8(6), 891–899 (2012). https://doi.org/10.1016/j.nano.2011.10.014
  37. D. Gao, R.C.H. Wong, Y. Wang, X. Guo, Z. Yang et al., Shifting the absorption to the near-infrared region and inducing a strong photothermal effect by encapsulating zinc (II) phthalocyanine in poly (lactic-co-glycolic acid)-hyaluronic acid nanoparticles. Acta Biomater. 116, 329–343 (2020). https://doi.org/10.1016/j.actbio.2020.08.042
  38. W. Zhang, W. Lin, X. Wang, C. Li, S. Liu et al., Hybrid nanomaterials of conjugated polymers and albumin for precise photothermal therapy. ACS Appl. Mater. Interfaces 11(1), 278–287 (2019). https://doi.org/10.1021/acsami.8b17922
  39. Z. Yang, Y. Wang, D. Gao, Y. Liu, X. Guo et al., immunogenic-cell-killing and immunosuppression-inhibiting nanomedicine. Bioactive Mater. 6(6), 1513–1527 (2020). https://doi.org/10.1016/j.bioactmat.2020.11.016
  40. H. Lin, S. Gao, C. Dai, Y. Chen, J. Shi, A two-dimensional biodegradable niobium carbide (MXene) for photothermal tumor eradication in NIR-I and NIR-II biowindows. J. Am. Chem. Soc. 139(45), 16235–16247 (2017). https://doi.org/10.1021/jacs.7b07818
  41. Q. Tian, F. Jiang, R. Zou, Q. Liu, Z. Chen et al., Hydrophilic Cu9S5 nanocrystals: a photothermal agent with a 25.7% heat conversion efficiency for photothermal ablation of cancer cells in vivo. ACS Nano 5(12), 9761–9771 (2011). https://doi.org/10.1021/nn203293t
  42. S. Müller, F. Sindikubwabo, T. Cañeque, A. Lafon, A. Versini et al., CD44 regulates epigenetic plasticity by mediating iron endocytosis. Nat. Chem. 12, 929–938 (2020). https://doi.org/10.1038/s41557-020-0513-5
  43. J. Li, K. Shi, Z.F. Sabet, W.J. Fu, H.G. Zhou et al., New power of self-assembling carbonic anhydrase inhibitor: Short peptide–constructed nanofibers inspire hypoxic cancer therapy. Sci. Adv. 5, eaax0937 (2019). https://doi.org/10.1126/sciadv.aax0937
  44. Z.H. Chen, Y. Saito, Y. Yoshida, E. Niki, Effect of oxygen concentration on free radical-induced cytotoxicity. Biosci., Biotechnol. Biochem. 72(6), 1491–1497 (2008). https://doi.org/10.1271/bbb.80002
  45. S. Angerani, N. Winssinger, Sense-and-release logic-gated molecular network responding to dimeric cell surface proteins. J. Am. Chem. Soc. 142, 12333–12340 (2020). https://doi.org/10.1021/jacs.0c04469
  46. V. Alterio, A.D. Fiore, K. D’Ambrosio, C.T. Supuran, G.D. Simone, Multiple binding modes of inhibitors to carbonic anhydrases: how to design specific drugs targeting 15 different isoforms? Chem. Rev. 112, 4421–4468 (2020). https://doi.org/10.1021/cr200176r
  47. D. Wei, Y. Yu, X. Zhang, Y. Wang, H. Chen et al., Breaking the intracellular redox balance with diselenium nanoparticles for maximizing chemotherapy efficacy on patient-derived xenograft models. ACS Nano 14(12), 16984–16996 (2020). https://doi.org/10.1021/acsnano.0c06190
  48. S. Shen, C. Zhu, D. Huo, M. Yang, J. Xue, Y. Xia, A hybrid nanomaterial for the controlled generation of free radicals and oxidative destruction of hypoxic cancer cells. Angew. Chem., Int. Ed. 56(30), 8801–8804 (2017). https://doi.org/10.1002/anie.201702898
  49. W. Xiao, S. Zheng, A. Yang, X. Zhang, P. Liu et al., Incidence and survival outcomes of breast cancer with synchronous hepatic metastases: A population-based study. J. Cancer 9(23), 4306–4313 (2018). https://doi.org/10.7150/jca.29190
  50. W. Xiao, S. Zheng, A. Yang, X. Zhang, Y. Zou et al., Breast cancer subtypes and the risk of distant metastasis at initial diagnosis: a population-based study. Cancer Manag. Res. 10, 5329 (2018). https://doi.org/10.2147/CMAR.S176763
  51. L. Jin, B. Han, E. Siegel, Y. Cui, A. Giuliano et al., Breast cancer lung metastasis: Molecular biology and therapeutic implications. Cancer Biol. Ther. 19(10), 858–868 (2018). https://doi.org/10.1080/15384047.2018.1456599
  52. J. Yang, X. Zhang, C. Liu, Z. Wang, L. Deng et al., Biologically modified nanoparticles as theranostic bionanomaterials. Prog. Mater. Sci. (2020). https://doi.org/10.1016/j.pmatsci.2020.100768
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