Issue

Vol. 15 (2023)

Artificial Macrophage with Hierarchical Nanostructure for Biomimetic Reconstruction of Antitumor Immunity

https://doi.org/10.1007/s40820-023-01193-4
Henan Zhao
Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, People’s Republic of China
Renyu Liu
Xiangya Hospital, Central South University, Changsha 410008, Hunan, People’s Republic of China
Liqiang Wang
Henan Province Industrial Technology Research Institute of Resources and Materials, School of Material Science and Engineering, Zhengzhou University, Zhengzhou 450001, Henan, People’s Republic of China
Feiying Tang
College of Chemical Engineering, Xiangtan University, Xiangtan 411105, Hunan, People’s Republic of China
Wansong Chen
Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, People’s Republic of China
You‑Nian Liu
Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha 410083, Hunan, People’s Republic of China

Corresponding Author: You‑Nian Liu

liuyounian@csu.edu.cn

Nano-Micro Letters, Vol. 15 (2023), Article Number: 216

Abstract

Artificial cells are constructed from synthetic materials to imitate the biological functions of natural cells. By virtue of nanoengineering techniques, artificial cells with designed biomimetic functions provide alternatives to natural cells, showing vast potential for biomedical applications. Especially in cancer treatment, the deficiency of immunoactive macrophages results in tumor progression and immune resistance. To overcome the limitation, a BaSO4@ZIF-8/transferrin (TRF) nanomacrophage (NMΦ) is herein constructed as an alternative to immunoactive macrophages. Alike to natural immunoactive macrophages, NMΦ is stably retained in tumors through the specific affinity of TRF to tumor cells. Zn2+ as an “artificial cytokine” is then released from the ZIF-8 layer of NMΦ under tumor microenvironment. Similar as proinflammatory cytokines, Zn2+ can trigger cell anoikis to expose tumor antigens, which are selectively captured by the BaSO4 cavities. Therefore, the hierarchical nanostructure of NMΦs allows them to mediate immunogenic death of tumor cells and subsequent antigen capture for T cell activation to fabricate long-term antitumor immunity. As a proof-of-concept, the NMΦ mimics the biological functions of macrophage, including tumor residence, cytokine release, antigen capture and immune activation, which is hopeful to provide a paradigm for the design and biomedical applications of artificial cells.


Highlights:
1 An artificial macrophage with hierarchical nanostructure (BaSO4@ZIF-8/TRF NMΦ) is constructed as an alternative to immunoactive macrophages.
2 The Zn2+ chemical messenger as an “artificial cytokine” is released from the artificial macrophage to induce tumor anoikis and enhance immunogenicity.
3 The artificial macrophage can efficiently capture tumor antigens for antigen presentation and T cell activation to fabricate long-term antitumor immunity, successfully mimicking the basic functions of natural immunoactive macrophage.

Keywords

Artificial macrophage Chemical messenger Hierarchical nanostructure Anoikis Antitumor immunotherapy
Zhao, Henan, Renyu Liu, Liqiang Wang, Feiying Tang, Wansong Chen, and You‑Nian Liu. 2023. “Artificial Macrophage With Hierarchical Nanostructure for Biomimetic Reconstruction of Antitumor Immunity”. Nano-Micro Letters 15 (September):216. https://doi.org/10.1007/s40820-023-01193-4.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. L.P. Lee, R. Szema, Inspirations from biological, optics for advanced phtonic systems. Science 310(5751), 1148–1150 (2005). https://doi.org/10.1126/science.1115248
  2. C. Yang, Y. Luo, H. Shen, M. Ge, J. Tang et al., Inorganic nanosheets facilitate humoral immunity against medical implant infections by modulating immune co-stimulatory pathways. Nat. Commun. 13(1), 4866 (2022). https://doi.org/10.1038/s41467-022-32405-x
  3. Y.-X. Zhu, Y. You, Z. Chen, D. Xu, W. Yue et al., Inorganic nanosheet-shielded probiotics: a self-adaptable oral delivery system for intestinal disease treatment. Nano Lett. 23(10), 4683–4692 (2023). https://doi.org/10.1021/acs.nanolett.3c00118
  4. W.Q. Ou, K.S. Nam, D.H. Park, J. Hwang, S.K. Ku et al., Artificial nanoscale erythrocytes from clinically relevant compounds for enhancing cancer immunotherapy. Nano-Micro Lett. 12(1), 90 (2020). https://doi.org/10.1007/s40820-020-00428-y
  5. Y. Elani, Interfacing living and synthetic cells as an emerging frontier in synthetic biology. Angew. Chem. Int. Ed. 60(11), 5602–5611 (2021). https://doi.org/10.1002/anie.202006941
  6. O.D. Toparlak, J. Zasso, S. Bridi, M. Dalla Serra, P. Macchi et al., Artificial cells drive neural differentiation. Sci. Adv. 6(38), eabb4920 (2020). https://doi.org/10.1126/sciadv.abb4920
  7. J. Li, S.J. Wang, X.Y. Lin, Y.B. Cao, Z.X. Cai et al., Red blood cell-mimic nanocatalyst triggering radical storm to augment cancer immunotherapy. Nano-Micro Lett. 14(1), 57 (2022). https://doi.org/10.1007/s40820-022-00801-z
  8. Y. Zheng, Y. Han, Q. Sun, Z. Li, Harnessing anti-tumor and tumor-tropism functions of macrophages via nanotechnology for tumor immunotherapy. Exploration (Beijing, China) 2(3), 20210166 (2022). https://doi.org/10.1002/exp.20210166
  9. T.A. Wynn, A. Chawla, J.W. Pollard, Macrophage biology in development, homeostasis and disease. Nature 496(7446), 445–455 (2013). https://doi.org/10.1038/nature12034
  10. C. Palena, J.L. Gulley, A rare insight into the immunosuppressive landscape of prostate cancer bone metastases. Cancer Cell 39(11), 1450–1452 (2021). https://doi.org/10.1016/j.ccell.2021.09.004
  11. M.L. Yang, C.H. Lin, Y.N. Wang, K. Chen, H.Y. Zhang et al., Identification of a cytokine-dominated immunosuppressive class in squamous cell lung carcinoma with implications for immunotherapy resistance. Genome Med. 14(1), 72 (2022). https://doi.org/10.1186/s13073-022-01079-x
  12. K. Ganesh, Z.K. Stadler, A. Cercek, R.B. Mendelsohn, J. Shia et al., Immunotherapy in colorectal cancer: rationale, challenges and potential. Nat. Rev. Gastroenterol. Hepatol. 16(6), 361–375 (2019). https://doi.org/10.1038/s41575-019-0126-x
  13. H. Lin, C. Yang, Y. Luo, M. Ge, H. Shen et al., Biomimetic nanomedicine-triggered in situ vaccination for innate and adaptive immunity activations for bacterial osteomyelitis treatment. ACS Nano 16(4), 5943–5960 (2022). https://doi.org/10.1021/acsnano.1c11132
  14. K. Pan, H. Farrukh, V. Chittepu, H.H. Xu, C.X. Pan et al., CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy. J. Exp. Clin. Cancer Res. 41(1), 119 (2022). https://doi.org/10.1186/s13046-022-02327-z
  15. E.C. Morris, S.S. Neelapu, T. Giavridis, M. Sadelain, Cytokine release syndrome and associated neurotoxicity in cancer immunotherapy. Nat. Rev. Immunol. 22(2), 85–96 (2022). https://doi.org/10.1038/s41577-021-00547-6
  16. D. Alizadeh, R.A. Wong, S. Gholamin, M. Maker, M. Aftabizadeh et al., IFN gamma is critical for CAR T cell-mediated myeloid activation and induction of endogenous immunity. Cancer Discov. 11(9), 2248–2265 (2021). https://doi.org/10.1158/2159-8290.Cd-20-1661
  17. A. Rodriguez-Garcia, R.C. Lynn, M. Poussin, M.A. Eiva, L.C. Shaw et al., CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy. Nat. Commun. 12(1), 877 (2021). https://doi.org/10.1038/s41467-021-20893-2
  18. H. Karoui, P.S. Patwal, B. Kumar, N. Martin, Chemical communication in artificial cells: basic concepts, design and challenges. Front. Mol. Biosci. 9, 880525 (2022). https://doi.org/10.3389/fmolb.2022.880525
  19. R. Noy, J.W. Pollard, Tumor-associated macrophages: from mechanisms to therapy. Immunity 41(1), 49–61 (2014). https://doi.org/10.1016/j.immuni.2014.06.010
  20. H.N. Zhao, L.Q. Wang, K. Zeng, J.H. Li, W.S. Chen et al., Nanomessenger-mediated signaling cascade for antitumor immunotherapy. ACS Nano 15(8), 13188–13199 (2021). https://doi.org/10.1021/acsnano.1c02765
  21. D. van Dinther, H. Veninga, S. Iborra, E.G.F. Borg, L. Hoogterp et al., Functional CD169 on macrophages mediates interaction with dendritic cells for CD8(+) T cell cross-priming. Cell Rep. 22(6), 1484–1495 (2018). https://doi.org/10.1016/j.celrep.2018.01.021
  22. S.B. Lee, J.E. Lee, S.J. Cho, J. Chin, S.K. Kim et al., Crushed gold shell nanops labeled with radioactive iodine as a theranostic nanoplatform for macrophage-mediated photothermal therapy. Nano-Micro Lett. 11(1), 36 (2019). https://doi.org/10.1007/s40820-019-0266-0
  23. D. Gaur, N.C. Dubey, B.P. Tripathi, Biocatalytic self-assembled synthetic vesicles and coacervates: from single compartment to artificial cells. Adv. Colloid Interface Sci. 299, 102556 (2022). https://doi.org/10.1016/j.cis.2021.102566
  24. M.D. Hunckler, A.J. Garca, Engineered biomaterials for enhanced function of insulin-secreting beta-cell organoids. Adv. Funct. Mater. 30(48), 2000134 (2020). https://doi.org/10.1002/adfm.202000134
  25. D. McMahon, Chemical messengers in development: a hypothesis. Science 185(4156), 1012–1021 (1974). https://doi.org/10.1126/science.185.4156.1012
  26. S. Bai, Y.L. Lan, S.Y. Fu, H.W. Cheng, Z.X. Lu et al., Connecting calcium-based nanomaterials and cancer: from diagnosis to therapy. Nano-Micro Lett. 14(1), 145 (2022). https://doi.org/10.1007/s40820-022-00894-6
  27. Z. Dai, Q.Y. Wang, J. Tang, M. Wu, H.Z. Li et al., Immune-regulating bimetallic metal-organic framework nanops designed for cancer immunotherapy. Biomaterials 280, 121261 (2022). https://doi.org/10.1016/j.biomaterials.2021.121261
  28. F. Gong, J.C. Xu, B. Liu, N.L. Yang, L. Cheng et al., Nanoscale CaH2 materials for synergistic hydrogen-immune cancer therapy. Chem 8(1), 268–286 (2022). https://doi.org/10.1016/j.chempr.2021.11.020
  29. X.G. Zhang, L.L. Cheng, Y. Lu, J.J. Tang, Q.J. Lv et al., A mxene-based bionic cascaded-enzyme nanoreactor for tumor phototherapy/enzyme dynamic therapy and hypoxia-activated chemotherapy. Nano-Micro Lett. 14(1), 22 (2022). https://doi.org/10.1007/s40820-021-00761-w
  30. G. Lu, S.Z. Li, Z. Guo, O.K. Farha, B.G. Hauser et al., Imparting functionality to a metal-organic framework material by controlled nanop encapsulation. Nat. Chem. 4(4), 310–316 (2012). https://doi.org/10.1038/nchem.1272
  31. M. Guilliams, P. Bruhns, Y. Saeys, H. Hammad, B.N. Lambrecht, The function of fc gamma receptors in dendritic cells and macrophages. Nat. Rev. Immunol. 14(2), 94–108 (2014). https://doi.org/10.1038/nri3582
  32. J. Yang, L. Wang, L. Huang, X. Che, Z. Zhang et al., Receptor-targeting nanomaterials alleviate binge drinking-induced neurodegeneration as artificial neurotrophins. Exploration (Beijing, China) 1(1), 61–74 (2021). https://doi.org/10.1002/exp.20210004
  33. J. Park, S.H. Wrzesinski, E. Stern, M. Look, J. Criscione et al., Combination delivery of TGF-beta inhibitor and Il-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy. Nat. Mater. 11(10), 895–905 (2012). https://doi.org/10.1038/nmat3355
  34. R. Feltham, K. Jamal, T. Tenev, G. Liccardi, I. Jaco et al., Mind bomb regulates cell death during TNF signaling by suppressing RIPK1’s cytotoxic potential. Cell Rep. 23(2), 470–484 (2018). https://doi.org/10.1016/j.celrep.2018.03.054
  35. A. Conod, M. Silvano, A.R.I. Altaba, On the origin of metastases: Induction of pro-metastatic states after impending cell death via ER stress, reprogramming, and a cytokine storm. Cell Rep. 38(10), 110490 (2022). https://doi.org/10.1016/j.celrep.2022.110490
  36. J. Tang, Y. Yang, J.J. Qu, W.H. Ban, H. Song et al., Mesoporous sodium four-coordinate aluminosilicate nanops modulate dendritic cell pyroptosis and activate innate and adaptive immunity. Chem. Sci. 13(29), 8507–8517 (2022). https://doi.org/10.1039/d1sc05319a
  37. B. Zhao, L. Li, L. Wang, C.Y. Wang, J.D. Yu et al., Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis. Genes Dev. 26(1), 54–68 (2012). https://doi.org/10.1101/gad.173435.111
  38. B. Bornstein, E.E. Zahavi, S. Gelley, M. Zoosman, S.P. Yaniv et al., Developmental axon pruning requires destabilization of cell adhesion by JNK signaling. Neuron 88(5), 926–940 (2015). https://doi.org/10.1016/j.neuron.2015.10.023
  39. K. Lei, R.J. Davis, JNK phosphorylation of BIM-related members of the Bcl2 family induces Bax-dependent apoptosis. Proc. Natl. Acad. Sci. USA 100(5), 2432–2437 (2003). https://doi.org/10.1073/pnas.0438011100
  40. X.X. Cheng, J. Wang, C.L. Liu, T.D. Jiang, N.Z. Yang et al., Zinc transporter SLC39A13/ZIP13 facilitates the metastasis of human ovarian cancer cells via activating src/fak signaling pathway. J. Exp. Clin. Cancer Res. 40(1), 199 (2021). https://doi.org/10.1186/s13046-021-01999-3
  41. S. Choi, C.C. Cui, Y.H. Luo, S.H. Kim, J.K. Ko et al., Selective inhibitory effects of zinc on cell proliferation in esophageal squamous cell carcinoma through orai1. Faseb J. 32(1), 404–416 (2018). https://doi.org/10.1096/fj.201700227RRR
  42. E.C. Vaquero, M. Edderkaoui, K.J. Nam, I. Gukovsky, S.J. Pandol et al., Extracellular matrix proteins protect pancreatic cancer cells from death via mitochondrial and nonmitochondrial pathways. Gastroenterology 125(4), 1188–1202 (2003). https://doi.org/10.1016/s0016-5085(03)01203-4
  43. S.M. Cardoso, C. Pereira, A.R. Oliveira, Mitochondrial function is differentially affected upon oxidative stress. Free Radical Bio. Med. 26(1–2), 3–13 (1999). https://doi.org/10.1016/s0891-5849(98)00205-6
  44. L.X. Huang, Y. Rong, X. Tang, K.Z. Yi, P. Qi et al., Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer. Mol. Cancer 21(1), 45 (2022). https://doi.org/10.1186/s12943-022-01515-x
  45. G. Yang, S.B. Lu, C. Li, F. Chen, J.S. Ni et al., Type I macrophage activator photosensitizer against hypoxic tumors. Chem. Sci. 12(44), 14773–14780 (2021). https://doi.org/10.1039/d1sc04124j
  46. L.J. Edgar, N. Kawasaki, C.M. Nycholat, J.C. Paulson, Targeted delivery of antigen to activated CD169(+) macrophages induces bias for expansion of CD8(+) T cells. Cell Chem. Biol. 26(1), 131–136 (2019). https://doi.org/10.1016/j.chembiol.2018.10.006
  47. V.N. Uversky, Barium Binding to Ef-hand Proteins and Potassium Channels, in Encyclopedia of Metalloproteins. ed. by R.H. Kretsinger, V.N. Uversky, E.A. Permyakov (Springer, New York, NY, 2013), pp.236–241
  48. T. Kumarevel, Barium and Protein–RNA Interactions, in Encyclopedia of Metalloproteins. ed. by R.H. Kretsinger, V.N. Uversky, E.A. Permyakov (Springer New York, New York, NY, 2013), pp.223–236
  49. C.L. Buchheit, K.J. Weigel, Z.T. Schafer, Opinion cancer cell survival during detachment from the ECM: multiple barriers to tumour progression. Nat. Rev. Cancer 14(9), 632–641 (2014). https://doi.org/10.1038/nrc3789
  50. A. Grosse-Wilde, C.J. Kemp, Metastasis suppressor function of tumor necrosis factor-related apoptosis-inducing ligand-r in mice: implications for trail-based therapy in humans? Cancer Res. 68(15), 6035–6037 (2008). https://doi.org/10.1158/0008-5472.Can-08-0078
  51. A. Mantovani, S. Sozzani, M. Locati, P. Allavena, A. Sica, Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 23(11), 549–555 (2002). https://doi.org/10.1016/s1471-4906(02)02302-5
  52. D. Gabrilovich, Fatal attraction: how macrophages participate in tumor metastases. J. Exp. Med. 212(7), 976–976 (2015). https://doi.org/10.1084/jem.2127insight1
Read More
Author biographies are not available.
Download this PDF file
PDF SUPPLEMENTARY FILE
Statistic
Read Counter : 2809 Download : 2094

Most read articles by the same author(s)