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Prodrug-loaded semiconducting polymer hydrogels for deep-tissue sono-immunotherapy of orthotopic glioblastoma.
Zhu, Liyun; Wang, Xing; Ding, Mengbin; Yu, Ningyue; Zhang, Yijing; Wu, Hongwei; Zhang, Qin; Liu, Jiansheng; Li, Jingchao.
Afiliação
  • Zhu L; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
  • Wang X; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
  • Ding M; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
  • Yu N; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
  • Zhang Y; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
  • Wu H; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
  • Zhang Q; Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. sabrina_1985@shu.edu.cn.
  • Liu J; Department of Neurology, Zhongshan-Xuhui Hospital, Fudan University, Shanghai 200032, China. drjianshengliu84@gmail.com.
  • Li J; State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China. wuhongwei@dhu.edu.cn.
Biomater Sci ; 11(20): 6823-6833, 2023 Oct 10.
Article em En | MEDLINE | ID: mdl-37623749
ABSTRACT
Although immunotherapy has achieved great success in the treatment of a variety of tumors, its efficacy for glioblastoma (GBM) is still limited. Both the immunosuppressive tumor microenvironment (TME) and poor penetration of immunotherapeutic agents into tumors contributed to the poor anti-glioma immunity. Herein, we develop an injectable prodrug-loaded hydrogel delivery system with sono-activatable properties for sonodynamic therapy (SDT)-triggered immunomodulation for GBM treatment. The prodrug alginate hydrogels (APN), which contain semiconducting polymer nanoparticles (SPNs) and the NLG919 prodrug linked by singlet oxygen (1O2)-cleavable linkers, are in situ formed via coordination of alginate solution with Ca2+ in the TME. SPNs serve as sonosensitizers to produce 1O2 upon ultrasound (US) irradiation for SDT. The generated 1O2 not only induce immunogenic cell death, but also break 1O2-cleavable linkers to precisely activate the NLG919 prodrug. Antitumor immunity is significantly amplified due to the reversal of immunosuppression mediated by indolamine 2,3-dioxygenase-dependent tryptophan metabolism. This smart prodrug hydrogel platform potently inhibits tumor growth in orthotopic glioma-bearing mice. Collectively, this work provides a sono-activatable hydrogel platform for precise sono-immunotherapy against GBM.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pró-Fármacos / Glioblastoma / Nanopartículas / Glioma / Neoplasias Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pró-Fármacos / Glioblastoma / Nanopartículas / Glioma / Neoplasias Limite: Animals Idioma: En Ano de publicação: 2023 Tipo de documento: Article