The combination of chemotherapy and immunotherapy motivates a potent immune system by triggering immunogenic cell death(ICD),showing great potential in inhibiting tumor growth and improving the immunosuppressive tumor microenvironment(ITM).However,the therapeutic effective-ness has been restricted by inferior drug bioavailability.Herein,we reported a universal bioresponsive doxorubicin(DOX)-based nanogel to achieve tumor-specific co-delivery of drugs.DOX-based mannose nanogels(DM NGs)was designed and choosed as an example to elucidate the mechanism of combined chemo-immunotherapy.As expected,the DM NGs exhibited prominent micellar stability,selective drug release and prolonged survival time,benefited from the enhanced tumor permeability and prolonged blood circulation.We discovered that the DOX delivered by DM NGs could induce powerful anti-tumor immune response facilitated by promoting ICD.Meanwhile,the released mannose from DM NGs was proved as a powerful and synergetic treatment for breast cancer in vitro and in vivo,via damaging the glucose metabolism in glycolysis and the tricarboxylic acid cycle.Overall,the regulation of tumor microenvironment with DOX-based nanogel is expected to be an effectual candidate strategy to overcome the current limitations of ICD-based immunotherapy,offering a paradigm for the exploitation of immunomodulatory nanomedicines.

Xianbin Ma;Shaochen Yang;Tian Zhang;Shuo Wang;Qichao Yang;Yao Xiao;Xiaoxiao Shi;Peng Xue;Yuejun Kang;Gang Liu;Zhi-Jun Sun;Zhigang Xu

Key Laboratory of Luminescence Analysis and Molecular Sensing(Southwest University),Ministry of Education,School of Materials and Energy & Chongqing Engineering Research Center for Micro-Nano Biomedical Materials and Devices,Southwest University,Chongqing 400715,China;The State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST) & Key Laboratory of Oral Biomedicine,Ministry of Education,School and Hospital of Stomatology,Wuhan University,Wuhan 430079,China;State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics & Center for Molecular Imaging and Translational Medicine,School of Public Health,Xiamen University,Xiamen 361102,China

药学学报（英文版）

[1]Xianbin Ma;Shaochen Yang;Tian Zhang;Shuo Wang;Qichao Yang;Yao Xiao;Xiaoxiao Shi;Peng Xue;Yuejun Kang;Gang Liu;Zhi-Jun Sun;Zhigang Xu-.Bioresponsive immune-booster-based prodrug nanogel for cancer immunotherapy)[J].药学学报（英文版）,2022(01):451-466

Bioresponsive,nanogel,bioresponsive,choosed

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