A polymer nanogel-based therapeutic nanovaccine for prophylaxis and direct treatment of tumors via a full-cycle immunomodulation

Yunqi Guo; Zhiqiang Wang; Gaoming Li; Mengsi Zhan; Tingting Xiao; Jianhong Wang; Jan C.M. van Hest; Xiangyang Shi; Mingwu Shen

Bioactive Materials (Jan 2025)

A polymer nanogel-based therapeutic nanovaccine for prophylaxis and direct treatment of tumors via a full-cycle immunomodulation

Yunqi Guo,
Zhiqiang Wang,
Gaoming Li,
Mengsi Zhan,
Tingting Xiao,
Jianhong Wang,
Jan C.M. van Hest,
Xiangyang Shi,
Mingwu Shen

Affiliations

Yunqi Guo: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China
Zhiqiang Wang: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China
Gaoming Li: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China
Mengsi Zhan: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China
Tingting Xiao: Institute of Frontier Medical Technology, College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, PR China
Jianhong Wang: Bio-Organic Chemistry, Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, 5600, MB, the Netherlands
Jan C.M. van Hest: Bio-Organic Chemistry, Department of Biomedical Engineering, Institute for Complex Molecular Systems (ICMS), Eindhoven University of Technology, Eindhoven, 5600, MB, the Netherlands; Corresponding author.
Xiangyang Shi: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China; Corresponding author.
Mingwu Shen: State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Biological Science and Medical Engineering, Donghua University, Shanghai, 201620, PR China; Corresponding author.

Journal volume & issue: Vol. 43
pp. 129 – 144

Abstract

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Construction of a cancer nanovaccine that can simultaneously activate immune cells and exert efficient tumor treatment still remains a challenge. Herein, we showcase a proof-of-concept demonstration of an advanced therapeutic nanovaccine formulation based on poly(N-vinylcaprolactam) nanogels (NGs) which were loaded with manganese dioxide (MnO2), the sonosensitizer chlorin e6 (Ce6), and the immune adjuvant cyclic GMP-AMP (cGAMP). The gels were furthermore coated with apoptotic cancer cell membranes (AM). On the one hand, the AM promoted the recognition of NGs by antigen presenting cells (APCs) in lymph nodes due to their enhanced immunogenicity, then the loaded Mn and cGAMP could mature APCs via stimulator of interferon genes (STING) activation for triggering immunity to prevent tumor growth. On the other hand, the NGs could selectively release Mn2+ for hydroxyl radical production and Ce6 to generate single oxygen under ultrasound irradiation of tumors, respectively, thereby exerting local chemodynamic/sonodynamic therapy to induce immunogenic cell death (ICD). Moreover, the Mn2+ could also activate STING in tumors to synergize with ICD for potentiated immune responses. Overall, the biomimetic NG-based therapeutic nanovaccine could directly evoke immune system, and also conduct local tumor treatment to further activate ICD, thus realizing a full-cycle immunomodulation (tumor killing for ICD/antigen production, and tumor cells/APCs immune activation) to tackle bilateral tumor growth.

Published in Bioactive Materials

ISSN: 2452-199X (Online)
Publisher: KeAi Communications Co., Ltd.
Country of publisher: China
LCC subjects: Technology: Electrical engineering. Electronics. Nuclear engineering: Materials of engineering and construction. Mechanics of materials; Science: Biology (General)
Website: https://www.keaipublishing.com/en/journals/bioactive-materials/

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