Yin Yuying, Wang Hao, Xue Jingqiang, Yin Chenlu, Xing Yixin, Gu Wei
School of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, P. R. China.
School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, P. R. China.
Adv Healthc Mater. 2023 Nov;12(29):e2301269. doi: 10.1002/adhm.202301269. Epub 2023 Aug 30.
Nanozymes mediated chemodynamic therapy (CDT) is a newly developed therapeutic modality with high specificity. The efficacy of CDT, however, still confronts challenges from the immune inhibitory tumor microenvironment (TME). It is thus of great significance to synergize CDT with immunotherapeutic interventions. Herein, this work reports the design and preparation of CpG loaded, Cu doped double layered hydroxides nanosheets (CpG/Cu-LDHs) as immuno-nanozymes to potentiate overall anti-tumor efficacy by synergizing CDT with immunogenic cell death (ICD)-activated local and systemic immune responses. Such cooperative CDT-immuno effect together with immunosuppressive TME remodeling capacity conferred by CpG/Cu-LDHs led to effective suppression of both treated primary tumor and untreated distant tumor on a mouse tumor model. Thereby, synergizing CDT with ICD-driven, in situ vaccine-like immunotherapy by immuno-nanozymes provides a novel and generalized paradigm for devising highly efficient and specific anti-tumor strategy without the use of external stimulations.
纳米酶介导的化学动力学疗法（CDT）是一种新开发的具有高特异性的治疗方式。然而，CDT的疗效仍面临来自免疫抑制性肿瘤微环境（TME）的挑战。因此，将CDT与免疫治疗干预措施协同使用具有重要意义。在此，本研究报告了负载CpG的铜掺杂双层氢氧化物纳米片（CpG/Cu-LDHs）作为免疫纳米酶的设计与制备，通过将CDT与免疫原性细胞死亡（ICD）激活的局部和全身免疫反应协同作用，增强整体抗肿瘤疗效。CpG/Cu-LDHs赋予的这种协同CDT-免疫效应以及免疫抑制性TME重塑能力，在小鼠肿瘤模型上有效抑制了已治疗的原发性肿瘤和未治疗的远处肿瘤。因此，通过免疫纳米酶将CDT与ICD驱动的原位疫苗样免疫疗法协同使用，为设计高效、特异性的抗肿瘤策略提供了一种新颖且通用的范例，而无需使用外部刺激。
