Journal Home > Volume 16 , Issue 1
Nano Research 2023, 16(1): 938-950 https://doi.org/10.1007/s12274-022-4809-1
Research Article | Issue | Published: 02 September 2022

Amoeba-inspired magnetic microgel assembly assisted by engineered dextran-binding protein for vaccination against life-threatening systemic infection

Show Author's Information Shuo Liu1,2,3,  Yan Zhao1,  Linpei Guo4,  Qilin Yu1,2( )
Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Research Center for Infectious Diseases, Nankai University, Tianjin 300350, China
College of Environmental Science and Engineering, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin 300350, China
Department of Urology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi 214002, China
Keywords:
vaccination, magnetic nanoparticle, dextran, microgel, systemic infection, engineered protein
Topics:
Vaccines
Cite this article:
Liu S, Zhao Y, Guo L, et al. Amoeba-inspired magnetic microgel assembly assisted by engineered dextran-binding protein for vaccination against life-threatening systemic infection. Nano Research, 2023, 16(1): 938-950. https://doi.org/10.1007/s12274-022-4809-1
Download citation
EndNote(RIS)
BibTeX

580

Views

39

Downloads

Citations

1

Crossref

1

WoS

1

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

Vaccination is critical for population protection from pathogenic infections. However, its efficiency is frequently compromised by a failure of antigen retention and presentation. Herein, we designed a dextran-binding protein DexBP, which is composed of the carbohydrate-binding domains of Trichoderma reesei cellobiohydrolases Cel6A and Cel7A, together with the sequence of the fluorescent protein mCherry. DexBP was further prepared by engineered Escherichia coli cells and grafted to magnetic nanoparticles. The magnetic nanoparticles were integrated with a dextran/poly(vinyl alcohol) framework and a reactive oxygen species-responsive linker, obtaining magnetic polymeric microgels for carrying pathogen antigen. Similar to amoeba aggregation, the microgels self-assembled to form aggregates and further induced dendritic cell aggregation. This step-by-step assembly retained antigens at lymph nodes, promoted antigen presentation, stimulated humoral immunity, and protected the mice from life-threatening systemic infections. This study developed a magnetic microgel-assembling platform for dynamically regulating immune response during protection of the body from dangerous infections.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

Amoeba-inspired magnetic microgel assembly assisted by engineered dextran-binding protein for vaccination against life-threatening systemic infection

Show Author's information Shuo Liu1,2,3, Yan Zhao1, Linpei Guo4, Qilin Yu1,2( )
Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, Department of Microbiology, College of Life Sciences, Nankai University, Tianjin 300071, China
Research Center for Infectious Diseases, Nankai University, Tianjin 300350, China
College of Environmental Science and Engineering, Tianjin Key Laboratory of Environmental Remediation and Pollution Control, Nankai University, Tianjin 300350, China
Department of Urology, The Affiliated Wuxi No.2 People’s Hospital of Nanjing Medical University, Wuxi 214002, China

Abstract

Vaccination is critical for population protection from pathogenic infections. However, its efficiency is frequently compromised by a failure of antigen retention and presentation. Herein, we designed a dextran-binding protein DexBP, which is composed of the carbohydrate-binding domains of Trichoderma reesei cellobiohydrolases Cel6A and Cel7A, together with the sequence of the fluorescent protein mCherry. DexBP was further prepared by engineered Escherichia coli cells and grafted to magnetic nanoparticles. The magnetic nanoparticles were integrated with a dextran/poly(vinyl alcohol) framework and a reactive oxygen species-responsive linker, obtaining magnetic polymeric microgels for carrying pathogen antigen. Similar to amoeba aggregation, the microgels self-assembled to form aggregates and further induced dendritic cell aggregation. This step-by-step assembly retained antigens at lymph nodes, promoted antigen presentation, stimulated humoral immunity, and protected the mice from life-threatening systemic infections. This study developed a magnetic microgel-assembling platform for dynamically regulating immune response during protection of the body from dangerous infections.

Keywords: vaccination, magnetic nanoparticle, dextran, microgel, systemic infection, engineered protein

References(48)

[1]

Kollmann, T. R.; Marchant, A.; Way, S. S. Vaccination strategies to enhance immunity in neonates. Science 2020, 368, 612–615.
DOI Google Scholar
[2]

Iwasaki, A.; Omer, S. B. Why and how vaccines work. Cell 2020, 183, 290–295.
DOI Google Scholar
[3]

Laupèze, B.; Del Giudice, G.; Doherty, M. T.; Van Der Most, R. Vaccination as a preventative measure contributing to immune fitness. npj Vaccines 2021, 6, 93.
DOI Google Scholar
[4]

Mascola, J. R.; Fauci, A. S. Novel vaccine technologies for the 21st century. Nat. Rev. Immunol. 2020, 20, 87–88.
DOI Google Scholar
[5]

Su, S.; Du, L. Y.; Jiang, S. B. Learning from the past: Development of safe and effective COVID-19 vaccines. Nat. Rev. Microbiol. 2021, 19, 211–219.
DOI Google Scholar
[6]

Sa-Nguanmoo, N.; Namdee, K.; Khongkow, M.; Ruktanonchai, U.; Zhao, Y. X.; Liang, X. J. Review: Development of SARS-CoV-2 immuno-enhanced COVID-19 vaccines with nano-platform. Nano Res. 2022, 15, 2196–2225.
DOI Google Scholar
[7]

Mendonça, S. A.; Lorincz, R.; Boucher, P.; Curiel, D. T. Adenoviral vector vaccine platforms in the SARS-CoV-2 pandemic. npj Vaccines 2021, 6, 97.
DOI Google Scholar
[8]

Li, S. X.; Feng, X. R.; Wang, J. X.; He, L.; Wang, C. X.; Ding, J. X.; Chen, X. S. Polymer nanoparticles as adjuvants in cancer immunotherapy. Nano Res. 2018, 11, 5769–5786.
DOI Google Scholar
[9]

Pulendran, B.; Arunachalam, P. S.; O’Hagan, D. T. Emerging concepts in the science of vaccine adjuvants. Nat. Rev. Drug Discov. 2021, 20, 454–475.
DOI Google Scholar
[10]

Orr, M. T.; Khandhar, A. P.; Seydoux, E.; Liang, H.; Gage, E.; Mikasa, T.; Beebe, E. L.; Rintala, N. D.; Persson, K. H.; Ahniyaz, A. et al. Reprogramming the adjuvant properties of aluminum oxyhydroxide with nanoparticle technology. npj Vaccines 2019, 4, 1.
DOI Google Scholar
[11]

He, X. D.; Zhou, S. Q.; Huang, W. C.; Seffouh, A.; Mabrouk, M. T.; Morgan, M. T.; Ortega, J.; Abrams, S. I.; Lovell, J. F. A potent cancer vaccine adjuvant system for particleization of short, synthetic CD8+ T cell epitopes. ACS Nano 2021, 15, 4357–4371.
DOI Google Scholar
[12]

Li, X. P.; He, X. F.; He, D. R.; Liu, Y.; Chen, K.; Yin, P. C. A polymeric co-assembly of subunit vaccine with polyoxometalates induces enhanced immune responses. Nano Res. 2022, 15, 4175–4180.
DOI Google Scholar
[13]

Fries, C. N.; Curvino, E. J.; Chen, J. L.; Permar, S. R.; Fouda, G. G.; Collier, J. H. Advances in nanomaterial vaccine strategies to address infectious diseases impacting global health. Nat. Nanotechnol. 2021, 16, 1–14.
DOI Google Scholar
[14]

Daly, A. C.; Riley, L.; Segura, T.; Burdick, J. A. Hydrogel microparticles for biomedical applications. Nat. Rev. Mater. 2020, 5, 20–43.
DOI Google Scholar
[15]

Nguyen, T. P. T.; Li, F. Y.; Shrestha, S.; Tuan, R. S.; Thissen, H.; Forsythe, J. S.; Frith, J. E. Cell-laden injectable microgels: Current status and future prospects for cartilage regeneration. Biomaterials 2021, 279, 121214.
DOI Google Scholar
[16]

Griffin, D. R. Archang, M. M.; Kuan, C. H.; Weaver, W. M.; Weinstein, J. S.; Feng, A. C.; Ruccia, A.; Sideris, E.; Ragkousis, V.; Koh, J. et al. Activating an adaptive immune response from a hydrogel scaffold imparts regenerative wound healing. Nat. Mater. 2021, 20, 560–569.
DOI Google Scholar
[17]

Pan, Y.; Qi, Y. X.; Li, X. Y.; Luan, S. F.; Huang, Y. B. Application of mannose-functionalized microgel as a novel vaccine delivery platform for subunit vaccines. Adv. Funct. Mater. 2021, 31, 2105742.
DOI Google Scholar
[18]

Gavilán, H.; Avugadda, S. K.; Fernández-Cabada, T.; Soni, N.; Cassani, M.; Mai, B. T.; Chantrell, R.; Pellegrino, T. Magnetic nanoparticles and clusters for magnetic hyperthermia: Optimizing their heat performance and developing combinatorial therapies to tackle cancer. Chem. Soc. Rev. 2021, 50, 11614–11667.
DOI Google Scholar
[19]

Liu, X. L.; Zhang, Y. F.; Wang, Y. Y.; Zhu, W. J.; Li, G. L.; Ma, X. W.; Zhang, Y. H.; Chen, S. Z.; Tiwari, S.; Shi, K. J. et al. Comprehensive understanding of magnetic hyperthermia for improving antitumor therapeutic efficacy. Theranostics 2020, 10, 3793–3815.
DOI Google Scholar
[20]

Xiong, J. Q.; Wu, M.; Chen, J. L.; Liu, Y. F.; Chen, Y. R.; Fan, G. L.; Liu, Y. Y.; Cheng, J. J; Wang, Z. H.; Wang, S. X. et al. Cancer-erythrocyte hybrid membrane-camouflaged magnetic nanoparticles with enhanced photothermal-immunotherapy for ovarian cancer. ACS Nano 2021, 15, 19756–19770.
DOI Google Scholar
[21]

Yu, Q. L.; Deng, T.; Lin, F. C.; Zhang, B.; Zink, J. I. Supramolecular assemblies of heterogeneous mesoporous silica nanoparticles to co-deliver antimicrobial peptides and antibiotics for synergistic eradication of pathogenic biofilms. ACS Nano 2020, 14, 5926–5937.
DOI Google Scholar
[22]

Chiang, C. S.; Lin, Y. J.; Lee, R.; Lai, Y. H.; Cheng, H. W.; Hsieh, C. H.; Shyu, W. C.; Chen, S. Y. Combination of fucoidan-based magnetic nanoparticles and immunomodulators enhances tumour-localized immunotherapy. Nat. Nanotechnol. 2018, 13, 746–754.
DOI Google Scholar
[23]

Chao, Y.; Chen, G. B.; Liang, C.; Xu, J.; Dong, Z. L.; Han, X.; Wang, C.; Liu, Z. Iron nanoparticles for low-power local magnetic hyperthermia in combination with immune checkpoint blockade for systemic antitumor therapy. Nano Lett. 2019, 19, 4287–4296.
DOI Google Scholar
[24]

Yu, Q. L.; Zhang, Y. M.; Liu, Y. H.; Xu, X.; Liu, Y. Magnetism and photo dual-controlled supramolecular assembly for suppression of tumor invasion and metastasis. Sci. Adv. 2018, 4, eaat2297.
DOI Google Scholar
[25]

Tero, A.; Takagi, S.; Saigusa, T.; Ito, K.; Bebber, D. P.; Fricker, M. D.; Yumiki, K.; Kobayashi, R.; Nakagaki, T. Rules for biologically inspired adaptive network design. Science 2010, 327, 439–442.
DOI Google Scholar
[26]

Ott, W.; Jobst, M. A.; Bauer, M. S.; Durner, E.; Milles, L. F.; Nash, M. A.; Gaub, H. E. Elastin-like polypeptide linkers for single-molecule force spectroscopy. ACS Nano 2017, 11, 6346–6354.
DOI Google Scholar
[27]

Zhao, Y.; Liu, S.; Shi, Z. S.; Zhu, H. Q.; Li, M. C.; Yu, Q. L. Pathogen infection-responsive nanoplatform targeting macrophage endoplasmic reticulum for treating life-threatening systemic infection. Nano Res. 2022, 15, 6243–6255.
DOI Google Scholar
[28]

Wang, H.; Mooney, D. J. Biomaterial-assisted targeted modulation of immune cells in cancer treatment. Nat. Mater. 2018, 17, 761–772.
DOI Google Scholar
[29]

Kim, J.; Li, W. A.; Choi, Y.; Lewin, S. A.; Verbeke, C. S.; Dranoff, G.; Mooney, D. J. Injectable, spontaneously assembling, inorganic scaffolds modulate immune cells in vivo and increase vaccine efficacy. Nat. Biotechnol. 2015, 33, 64–72.
DOI Google Scholar
[30]

Zhou, W. X.; Chen, X. L.; Zhou, Y.; Shi, S.; Liang, C.; Yu, X. J.; Chen, H. Y.; Guo, Q.; Zhang, Y. W. et al. Exosomes derived from immunogenically dying tumor cells as a versatile tool for vaccination against pancreatic cancer. Biomaterials 2022, 280, 121306.
DOI Google Scholar
[31]

Nicolas-Boluda, A.; Yang, Z. J.; Guilbert, T.; Fouassier, L.; Carn, F.; Gazeau, F.; Pileni, M. P. Self-assemblies of Fe3O4 nanocrystals: Toward nanoscale precision of photothermal effects in the tumor microenvironment. Adv. Funct. Mater. 2021, 31, 2006824.
DOI Google Scholar
[32]

Antman-Passig, M.; Giron, J.; Karni, M.; Motiei, M.; Schori, H.; Shefi, O. Magnetic assembly of a multifunctional guidance conduit for peripheral nerve repair. Adv. Funct. Mater. 2021, 31, 2010837.
DOI Google Scholar
[33]

Zhao, H.; Huang, J.; Li, Y.; Lv, X. J.; Zhou, H. T.; Wang, H. R.; Xu, Y. Y.; Wang, C.; Wang, J.; Liu, Z. ROS-scavenging hydrogel to promote healing of bacteria infected diabetic wounds. Biomaterials 2020, 258, 120286.
DOI Google Scholar
[34]

Li, Z. H.; Zhu, D. S.; Hui, Q.; Bi, J. N.; Yu, B. J.; Huang, Z.; Hu, S. Q.; Wang, Z. Z.; Caranasos, T.; Rossi, J. et al. Injection of ROS-responsive hydrogel loaded with basic fibroblast growth factor into the pericardial cavity for heart repair. Adv. Funct. Mater. 2021, 31, 2004377.
DOI Google Scholar
[35]

Ruan, H. T.; Hu, Q. Y.; Wen, D.; Chen, Q.; Chen, G. J.; Lu, Y. F.; Wang, J. Q.; Cheng, H.; Lu, W. Y.; Gu, Z. A dual-bioresponsive drug-delivery depot for combination of epigenetic modulation and immune checkpoint blockade. Adv. Mater. 2019, 31, 1806957.
DOI Google Scholar
[36]

Forman, H. J.; Torres, M. Reactive oxygen species and cell signaling: Respiratory burst in macrophage signaling. Am. J. Respir. Crit. Care. Med. 2002, 166, S4–S8.
DOI Google Scholar
[37]

Steinman, R. M. Decisions about dendritic cells: Past, present, and future. Annu. Rev. Immunol. 2012, 30, 1–22.
DOI Google Scholar
[38]

Wculek, S. K.; Cueto, F. J.; Mujal, A. M.; Melero, I.; Krummel, M. F.; Sancho, D. Dendritic cells in cancer immunology and immunotherapy. Nat. Rev. Immunol. 2020, 20, 7–24.
DOI Google Scholar
[39]

Yin, X. Y.; Chen, S. T.; Eisenbarth, S. C. Dendritic cell regulation of T Helper cells. Annu. Rev. Immunol. 2021, 39, 759–790.
DOI Google Scholar
[40]

El-Sayed, N.; Korotchenko, E.; Scheiblhofer, S.; Weiss, R.; Schneider, M. Functionalized multifunctional nanovaccine for targeting dendritic cells and modulation of immune response. Int. J. Pharm. 2021, 593, 120123.
DOI Google Scholar
[41]

Vetvicka, V. Glucan-immunostimulant, adjuvant, potential drug. World J. Clin. Oncol. 2011, 2, 115–119.
DOI Google Scholar
[42]

Nauseef, W. M. How human neutrophils kill and degrade microbes: An integrated view. Immunol. Rev. 2007, 219, 88–102.
DOI Google Scholar
[43]

Germain, R. N. MHC-dependent antigen processing and peptide presentation: Providing ligands for T lymphocyte activation. Cell 1994, 76, 287–299.
DOI Google Scholar
[44]

Itano, A. A.; Jenkins, M. K. Antigen presentation to naive CD4 T cells in the lymph node. Nat. Immunol. 2003, 4, 733–739.
DOI Google Scholar
[45]

Jhunjhunwala, S.; Hammer, C.; Delamarre, L. Antigen presentation in cancer: Insights into tumour immunogenicity and immune evasion. Nat. Rev. Cancer 2021, 21, 298–312.
DOI Google Scholar
[46]

Jawale, C. V.; Ramani, K.; Li, D. D.; Coleman, B. M.; Oberoi, R. S.; Kupul, S.; Lin, L.; Desai, J. V.; Delgoffe, G. M.; Lionakis, M. S. et al. Restoring glucose uptake rescues neutrophil dysfunction and protects against systemic fungal infection in mouse models of kidney disease. Sci. Transl. Med. 2020, 12, eaay5691.
DOI Google Scholar
[47]

Peng, L. P.; Wei, H. A.; Tian, L.; Xu, J. C.; Li, M. C.; Yu, Q. L. Phospholipid/protein co-mediated assembly of Cu2O nanoparticles for specific inhibition of growth and biofilm formation of pathogenic fungi. Sci. China Mater. 2021, 64, 759–768.
DOI Google Scholar
[48]

Boniche, C.; Rossi, S. A.; Kischkel, B.; Barbalho, F. V.; Moura, A. N. D.; Nosanchuk, J. D.; Travassos, L. R.; Taborda, C. P. Immunotherapy against systemic fungal infections based on monoclonal antibodies. J. Fungi 2020, 6, 31.
DOI Google Scholar
Video
12274_2022_4809_MOESM2_ESM.mp4
12274_2022_4809_MOESM3_ESM.mp4
File
12274_2022_4809_MOESM1_ESM.pdf (763.9 KB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 07 May 2022
Revised: 25 July 2022
Accepted: 25 July 2022
Published: 02 September 2022
Issue date: January 2023

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 3217010793 and 31870139), Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project (No. TSBICIP-KJGG-006), the Natural Science Foundation of Tianjin (No. 19JCZDJC33800), and the Fundamental Research Funds for the Central Universities.

Return