Journal Home > Volume 16 , Issue 8
Nano Research 2023, 16(8): 11206-11215 https://doi.org/10.1007/s12274-023-5839-z
Research Article | Issue | Published: 10 June 2023

A single magnetic nanoplatform-mediated combination therapy of immune checkpoint silencing and magnetic hyperthermia for enhanced anti-cancer immunity

Show Author's Information Zhiyu Yang1,2,4,  Xiaoya Guo1,2,4,  Meng Meng1,2,4,  Tong Li1,2,4,  Huapan Fang3,5( ),  Zhaohui Tang1,2,4,  Huayu Tian1,2,3,4,5( ),  Xuesi Chen1,2,4
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China
Keywords:
gene therapy, cancer immunotherapy, magnetic nanoclusters, immune checkpoint silencing, magnetic hyperthermia therapy
Topics:
Immunology
Cite this article:
Yang Z, Guo X, Meng M, et al. A single magnetic nanoplatform-mediated combination therapy of immune checkpoint silencing and magnetic hyperthermia for enhanced anti-cancer immunity. Nano Research, 2023, 16(8): 11206-11215. https://doi.org/10.1007/s12274-023-5839-z
Download citation
EndNote(RIS)
BibTeX

662

Views

60

Downloads

Citations

1

Crossref

2

WoS

2

Scopus

0

CSCD

Abstract Full text Electronic supplementary material About this article

As a revolutionary cancer treatment strategy, immunotherapy has attracted great attention. However, the effect of immunotherapy such as immune checkpoint blockade (ICB) is usually limited by insufficient immune response in the body. Herein, a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids, which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy (MHT). The silencing of immune checkpoints together with MHT-induced immunogenic cell death (ICD) effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system. This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo, greatly inhibiting tumor growth, metastasis and recurrence.


menu
Abstract
Full text
Outline
Electronic supplementary material
About this article

A single magnetic nanoplatform-mediated combination therapy of immune checkpoint silencing and magnetic hyperthermia for enhanced anti-cancer immunity

Show Author's information Zhiyu Yang1,2,4, Xiaoya Guo1,2,4, Meng Meng1,2,4, Tong Li1,2,4, Huapan Fang3,5( ), Zhaohui Tang1,2,4, Huayu Tian1,2,3,4,5( ), Xuesi Chen1,2,4
Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China
School of Applied Chemistry and Engineering, University of Science and Technology of China, Hefei 230026, China
State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China
Jilin Biomedical Polymers Engineering Laboratory, Changchun 130022, China
Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen 361005, China

Abstract

As a revolutionary cancer treatment strategy, immunotherapy has attracted great attention. However, the effect of immunotherapy such as immune checkpoint blockade (ICB) is usually limited by insufficient immune response in the body. Herein, a polycation-based magnetic nanocluster platform was developed to load therapeutic nucleic acids, which could achieve gene therapy-mediated ICB and efficient magnetic hyperthermia therapy (MHT). The silencing of immune checkpoints together with MHT-induced immunogenic cell death (ICD) effectively alleviated the immune escape of cancer cells and significantly enhanced the visibility of cancer cells to the immune system. This combined treatment strategy activated a strong adaptive anti-cancer immune response in vivo, greatly inhibiting tumor growth, metastasis and recurrence.

Keywords: gene therapy, cancer immunotherapy, magnetic nanoclusters, immune checkpoint silencing, magnetic hyperthermia therapy

References(43)

[1]

Mellman, I.; Coukos, G.; Dranoff, G. Cancer immunotherapy comes of age. Nature 2011, 480, 480–489.
DOI Google Scholar
[2]

Blankenstein, T.; Coulie, P. G.; Gilboa, E.; Jaffee, E. M. The determinants of tumour immunogenicity. Nat. Rev. Cancer 2012, 12, 307–313.
DOI Google Scholar
[3]

Meng, J. L.; Zhang, P. S.; Chen, Q. Z.; Wang, Z. H.; Gu, Y.; Ma, J.; Li, W.; Yang, C.; Qiao, Y. Y.; Hou, Y. et al. Two-pronged intracellular co-delivery of antigen and adjuvant for synergistic cancer immunotherapy. Adv. Mater. 2022, 34, e2202168.
DOI Google Scholar
[4]
Wang, M. Y.; Wang, Y. F.; Mu, Y. T.; Yang, F. X.; Yang, Z. B.; Liu, Y. X.; Huang, L. L.; Liu, S.; Guan, X. G.; Xie, Z. G. et al. Engineering SIRPα cellular membrane-based nanovesicles for combination immunotherapy. Nano Res., in press, DOI: 10.1007/s12274-023-5397-4.
[5]

Xu, J. L.; Ma, Q. L.; Zhang, Y.; Fei, Z. Y.; Sun, Y. F.; Fan, Q.; Liu, B.; Bai, J. Y.; Yu, Y.; Chu, J. H. et al. Yeast-derived nanoparticles remodel the immunosuppressive microenvironment in tumor and tumor-draining lymph nodes to suppress tumor growth. Nat. Commun. 2022, 13, 110.
DOI Google Scholar
[6]

Xu, Y. D.; Ma, S.; Zhao, J. Y.; Si, X. H.; Huang, Z. C.; Zhang, Y.; Song, W. T.; Tang, Z. H.; Chen, X. S. Trinity immune enhancing nanoparticles for boosting antitumor immune responses of immunogenic chemotherapy. Nano Res. 2022, 15, 1183–1192.
DOI Google Scholar
[7]

Feng, Y. J.; Wu, J. Y.; Chen, J.; Lin, L.; Zhang, S. J.; Yang, Z. Y.; Sun, P. J.; Li, Y. H.; Tian, H. Y.; Chen, X. S. Targeting dual gene delivery nanoparticles overcomes immune checkpoint blockade induced adaptive resistance and regulates tumor microenvironment for improved tumor immunotherapy. Nano Today 2021, 38, 101194.
DOI Google Scholar
[8]

Yue, W. W.; Chen, L.; Yu, L. D.; Zhou, B. G.; Yin, H. H.; Ren, W. W.; Liu, C.; Guo, L. H.; Zhang, Y. F.; Sun, L. P. et al. Checkpoint blockade and nanosonosensitizer-augmented noninvasive sonodynamic therapy combination reduces tumour growth and metastases in mice. Nat. Commun. 2019, 10, 2025.
DOI Google Scholar
[9]

Fang, H. P.; Guo, Z. P.; Chen, J.; Lin, L.; Hu, Y. Y.; Li, Y. H.; Tian, H. Y.; Chen, X. S. Combination of epigenetic regulation with gene therapy-mediated immune checkpoint blockade induces anti-tumour effects and immune response in vivo. Nat. Commun. 2021, 12, 6742.
DOI Google Scholar
[10]

Xu, F.; Fei, Z. Y.; Dai, H. X.; Xu, J. L.; Fan, Q.; Shen, S. F.; Zhang, Y.; Ma, Q. L.; Chu, J. C.; Peng, F. et al. Mesenchymal stem cell-derived extracellular vesicles with high PD-L1 expression for autoimmune diseases treatment. Adv. Mater. 2022, 34, e2106265.
DOI Google Scholar
[11]

Tang, H. L.; Xu, X. J.; Chen, Y. X.; Xin, H. H.; Wan, T.; Li, B. W.; Pan, H. M.; Li, D.; Ping, Y. Reprogramming the tumor microenvironment through second-near-infrared-window photothermal genome editing of PD-L1 mediated by supramolecular gold nanorods for enhanced cancer immunotherapy. Adv. Mater. 2021, 33, e2006003.
DOI Google Scholar
[12]

Yang, Z. Y.; Guo, Z. P.; Tian, H. Y.; Chen, X. S. Enhancers in polymeric nonviral gene delivery systems. VIEW 2021, 2, 20200072.
DOI Google Scholar
[13]

Hong, T.; Shen, X. Y.; Syeda, M. Z.; Zhang, Y.; Sheng, H. N.; Zhou, Y. P.; Xu, J. M.; Zhu, C. J.; Li, H. J.; Gu, Z. et al. Recent advances of bioresponsive polymeric nanomedicine for cancer therapy. Nano Res. 2023, 16, 2660–2671.
DOI Google Scholar
[14]

Vaughan, H. J.; Green, J. J.; Tzeng, S. Y. Cancer-targeting nanoparticles for combinatorial nucleic acid delivery. Adv. Mater. 2020, 32, e1901081.
DOI Google Scholar
[15]

Lostalé-Seijo, I.; Montenegro, J. Synthetic materials at the forefront of gene delivery. Nat. Rev. Chem. 2018, 2, 258–277.
DOI Google Scholar
[16]

Kumar, R.; Santa Chalarca, C. F.; Bockman, M. R.; Bruggen, C. V.; Grimme, C. J.; Dalal, R. J.; Hanson, M. G.; Hexum, J. K.; Reineke, T. M. Polymeric delivery of therapeutic nucleic acids. Chem. Rev. 2021, 121, 11527–11652.
DOI Google Scholar
[17]

Li, T. L.; Song, R. D.; Sun, F.; Saeed, M.; Guo, X. Z.; Ye, J. Y.; Chen, F. M.; Hou, B.; Zhu, Q. R.; Wang, Y. J. et al. Bioinspired magnetic nanocomplexes amplifying STING activation of tumor-associated macrophages to potentiate cancer immunotherapy. Nano Today 2022, 43, 101400.
DOI Google Scholar
[18]

Fang, Y. F.; He, Y.; Wu, C. H.; Zhang, M.; Gu, Z. Y.; Zhang, J. X.; Liu, E. G.; Xu, Q.; Asrorov, A. M.; Huang, Y. Z. Magnetism-mediated targeting hyperthermia-immunotherapy in “cold” tumor with CSF1R inhibitor. Theranostics 2021, 11, 6860–6872.
DOI Google Scholar
[19]

Galluzzi, L.; Buqué, A.; Kepp, O.; Zitvogel, L.; Kroemer, G. Immunogenic cell death in cancer and infectious disease. Nat. Rev. Immunol. 2017, 17, 97–111.
DOI Google Scholar
[20]

Liu, X. L.; Zheng, J. J.; Sun, W.; Zhao, X.; Li, Y.; Gong, N. Q.; Wang, Y. Y.; Ma, X. W.; Zhang, T. B.; Zhao, L. Y. et al. Ferrimagnetic vortex nanoring-mediated mild magnetic hyperthermia imparts potent immunological effect for treating cancer metastasis. ACS Nano 2019, 13, 8811–8825.
DOI Google Scholar
[21]

Yi, Y. F.; Yu, M.; Feng, C.; Hao, H. S.; Zeng, W. W.; Lin, C. C.; Chen, H. Z.; Lv, F.; Zhu, D. W.; Ji, X. Y. et al. Transforming “cold” tumors into “hot” ones via tumor-microenvironment-responsive siRNA micelleplexes for enhanced immunotherapy. Matter 2022, 5, 2285–2305.
DOI Google Scholar
[22]

Li, W. X.; Xie, L. S.; Ju, Y.; Zhang, Z.; Li, B.; Li, J.; Sang, W.; Wang, G. H.; Tian, H.; Dai, Y. L. A “three musketeers” tactic for inclining interferon-γ as a comrade-in-arm to reinforce the synergistic-tumoricidal therapy. Nano Res. 2022, 15, 3458–3470.
DOI Google Scholar
[23]

Sen, S.; Won, M.; Levine, M. S.; Noh, Y.; Sedgwick, A. C.; Kim, J. S.; Sessler, J. L.; Arambula, J. F. Metal-based anticancer agents as immunogenic cell death inducers: The past, present, and future. Chem. Soc. Rev. 2022, 51, 1212–1233.
DOI Google Scholar
[24]

Liu, Z. Y.; Xu, X. T.; Liu, K. N.; Zhang, J. T.; Ding, D.; Fu, R. Immunogenic cell death in hematological malignancy therapy. Adv. Sci. 2023, 10, e2207475.
DOI Google Scholar
[25]

Qi, J.; Jin, F. Y.; You, Y. C.; Du, Y.; Liu, D.; Xu, X. L.; Wang, J.; Zhu, L. W.; Chen, M. J.; Shu, G. F. et al. Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles. Nat. Commun. 2021, 12, 4755.
DOI Google Scholar
[26]

Huang, Z. S.; Wang, Y. X.; Yao, D.; Wu, J. H.; Hu, Y. Q.; Yuan, A. H. Nanoscale coordination polymers induce immunogenic cell death by amplifying radiation therapy mediated oxidative stress. Nat. Commun. 2021, 12, 145.
DOI Google Scholar
[27]

Ma, Y. C.; Zhang, Y. X.; Li, X. Q.; Zhao, Y. Y.; Li, M.; Jiang, W.; Tang, X. F.; Dou, J. X.; Lu, L. G.; Wang, F. et al. Near-infrared II phototherapy induces deep tissue immunogenic cell death and potentiates cancer immunotherapy. ACS Nano 2019, 13, 11967–11980.
DOI Google Scholar
[28]

Shen, W.; Zhang, Y.; Wan, P. Q.; An, L.; Zhang, P.; Xiao, C. S.; Chen, X. S. Antineoplastic drug-free anticancer strategy enabled by host-defense-peptides-mimicking synthetic polypeptides. Adv. Mater. 2020, 32, e2001108.
Google Scholar
[29]
Yan, X.; Sun, T. C.; Song, Y. H.; Peng, W.; Xu, Y. J.; Luo, G. Y.; Li, M.; Chen, S.; Fang, W. W.; Dong, L. et al. In situ thermal-responsive magnetic hydrogel for multidisciplinary therapy of hepatocellular carcinoma. Nano Lett. 2022, 22, 2251–2260.
[30]

Song, Y. H.; Li, D. D.; Lu, Y.; Jiang, K.; Yang, Y.; Xu, Y. J.; Dong, L.; Yan, X.; Ling, D. S.; Yang, X. Z. et al. Ferrimagnetic mPEG-b-PHEP copolymer micelles loaded with iron oxide nanocubes and emodin for enhanced magnetic hyperthermia-chemotherapy. Natl. Sci. Rev. 2020, 7, 723–736.
DOI Google Scholar
[31]

Ximendes, E.; Marin, R.; Shen, Y. L.; Ruiz, D.; Gómez-Cerezo, D.; Rodríguez-Sevilla, P.; Lifante, J.; Viveros-Méndez, P. X.; Gámez, F.; García-Soriano, D. et al. Infrared-emitting multimodal nanostructures for controlled in vivo magnetic hyperthermia. Adv. Mater. 2021, 33, e2100077.
DOI Google Scholar
[32]

Wu, H. A.; Liu, L.; Song, L. N.; Ma, M.; Gu, N.; Zhang, Y. Enhanced tumor synergistic therapy by injectable magnetic hydrogel mediated generation of hyperthermia and highly toxic reactive oxygen species. ACS Nano 2019, 13, 14013–14023.
DOI Google Scholar
[33]

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
[34]

Balakrishnan, P. B.; Silvestri, N.; Fernandez-Cabada, T.; Marinaro, F.; Fernandes, S.; Fiorito, S.; Miscuglio, M.; Serantes, D.; Ruta, S.; Livesey, K. et al. Exploiting unique alignment of cobalt ferrite nanoparticles, mild hyperthermia, and controlled intrinsic cobalt toxicity for cancer therapy. Adv. Mater. 2020, 32, e2003712.
DOI Google Scholar
[35]

Carter, T. J.; Agliardi, G.; Lin, F. Y.; Ellis, M.; Jones, C.; Robson, M.; Richard-Londt, A.; Southern, P.; Lythgoe, M.; Zaw Thin, M. et al. Potential of magnetic hyperthermia to stimulate localized immune activation. Small 2021, 17, e2005241.
DOI Google Scholar
[36]

Panday, R.; Abdalla, A. M. E.; Yu, M.; Li, X. H.; Ouyang, C. X.; Yang, G. Functionally modified magnetic nanoparticles for effective siRNA delivery to prostate cancer cells in vitro. J. Biomater. Appl. 2020, 34, 952–964.
DOI Google Scholar
[37]

Chiu-Lam, A.; Staples, E.; Pepine, C. J.; Rinaldi, C. Perfusion, cryopreservation, and nanowarming of whole hearts using colloidally stable magnetic cryopreservation agent solutions. Sci. Adv. 2021, 7, eabe3005.
DOI Google Scholar
[38]

Zhao, X.; Meng, Z. G.; Wang, Y.; Chen, W. J.; Sun, C. J.; Cui, B.; Cui, J. H.; Yu, M. L.; Zeng, Z. H.; Guo, S. D. et al. Pollen magnetofection for genetic modification with magnetic nanoparticles as gene carriers. Nat. Plants 2017, 3, 956–964.
DOI Google Scholar
[39]

Tay, A. The benefits of going small: Nanostructures for mammalian cell transfection. ACS Nano 2020, 14, 7714–7721.
DOI Google Scholar
[40]

Zhang, T. Y.; Xu, Q. H.; Huang, T.; Ling, D. S.; Gao, J. Q. New insights into biocompatible iron oxide nanoparticles: A potential booster of gene delivery to stem cells. Small 2020, 16, e2001588.
DOI Google Scholar
[41]

Jiang, P. P.; Zhu, Y.; Kang, K.; Luo, B.; He, J.; Wu, Y. Protein corona of magnetic PEI/siRNA complex under the influence of a magnetic field improves transfection efficiency via complement and coagulation cascades. J. Mater. Chem. B 2019, 7, 4207–4216.
DOI Google Scholar
[42]

Du, M.; Chen, Y. H.; Tu, J. W.; Liufu, C.; Yu, J. S.; Yuan, Z.; Gong, X. J.; Chen, Z. Y. Ultrasound responsive magnetic mesoporous silica nanoparticle-loaded microbubbles for efficient gene delivery. ACS Biomater. Sci. Eng. 2020, 6, 2904–2912.
DOI Google Scholar
[43]

Pan, J.; Hu, P.; Guo, Y. D.; Hao, J. N.; Ni, D. L.; Xu, Y. Y.; Bao, Q. Q.; Yao, H. L.; Wei, C. Y.; Wu, Q. S. et al. Combined magnetic hyperthermia and immune therapy for primary and metastatic tumor treatments. ACS Nano 2020, 14, 1033–1044.
DOI Google Scholar
File
12274_2023_5839_MOESM1_ESM.pdf (2.4 MB)
Publication history
Copyright
Acknowledgements

Publication history

Received: 29 March 2023
Revised: 08 May 2023
Accepted: 11 May 2023
Published: 10 June 2023
Issue date: August 2023

Copyright

© Tsinghua University Press 2023

Acknowledgements

Acknowledgements

The authors are thankful to National Natural Science Foundation of China (Nos. 51925305, 51873208, 51833010, and 52203183), the National Key Research and Development Program of China (No. 2021YFB3800900), and the talent cultivation project Funds for the Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (No. HRTP-[2022]52).

Return