MnO2 Nanoflowers Induce Immunogenic Cell Death under Nutrient Deprivation: Enabling an Orchestrated Cancer Starvation‐Immunotherapy,Advanced Science

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MnO2 Nanoflowers Induce Immunogenic Cell Death under Nutrient Deprivation: Enabling an Orchestrated Cancer Starvation‐Immunotherapy
Advanced Science ( IF 14.3 ) Pub Date : 2020-12-31 , DOI: 10.1002/advs.202002667
Yannan Yang ₁ , Zhengying Gu ₁ , Jie Tang ₁ , Min Zhang _{1,

2} , Yang Yang ₁ , Hao Song ₁ , Chengzhong Yu _{1,

2}

Affiliation

MnO₂ nanoparticles have been widely employed in cancer immunotherapy, playing a subsidiary role in assisting immunostimulatory drugs by improving their pharmacokinetics and/or creating a favorable microenvironment. Here, the stereotype of the subsidiary role of MnO₂ nanoparticles in cancer immunotherapy is challenged. This study unravels an intrinsic immunomodulatory property of MnO₂ nanoparticles as a unique nutrient‐responsive immunogenic cell death (ICD) inducer, capable of directly modulating immunosurveillance toward tumor cells. MnO₂ nanoflowers (MNFs) constructed via a one pot self‐assembly approach selectively induce ICD to nutrient‐deprived but not nutrient‐replete cancer cells, which is confirmed by the upregulated damage associated molecular patterns in vitro and a prophylactic vaccination in vivo. The underlying mechanism of the MNFs‐mediated selective ICD induction is likely associated with the concurrently upregulated oxidative stress and autophagy. Built on their unique immunomodulatory properties, an innovative nanomaterials orchestrated cancer starvation‐immunotherapy is successfully developed, which is realized by the in situ vaccination with MNFs and vascular disrupting agents that cut off intratumoral nutrient supply, eliciting potent efficacy for suppressing local and distant tumors. These findings open up a new avenue toward biomedical applications of MnO₂ materials, enabling an innovative therapeutics paradigm with great clinical significance.

中文翻译：

MnO2 纳米花在营养剥夺下诱导免疫原性细胞死亡：实现精心策划的癌症饥饿免疫疗法

MnO ₂纳米颗粒已广泛应用于癌症免疫治疗，通过改善免疫刺激药物的药代动力学和/或创造有利的微环境，在辅助免疫刺激药物方面发挥辅助作用。_{在此，MnO 2}纳米颗粒在癌症免疫治疗中的辅助作用的刻板印象受到了挑战。_{这项研究揭示了 MnO 2}纳米粒子作为一种独特的营养响应性免疫原性细胞死亡 (ICD) 诱导剂的内在免疫调节特性，能够直接调节对肿瘤细胞的免疫监视。通过一锅自组装方法构建的 MnO 2 纳米花 (MNF) 选择性诱导 ICD 进入营养缺乏但不是营养充足的癌细胞，这一点通过体外与分子模式相关的损伤上调和体内预防性疫苗接种得到证实_。MNF 介导的选择性 ICD 诱导的潜在机制可能与同时上调的氧化应激和自噬有关。基于其独特的免疫调节特性，成功开发了一种创新的纳米材料精心策划的癌症饥饿免疫疗法，通过原位接种MNF和血管破坏剂来切断肿瘤内的营养供应，从而产生抑制局部和远处肿瘤的有效功效。_{这些发现为MnO 2}材料的生物医学应用开辟了新途径，实现了具有重大临床意义的创新治疗范例。

更新日期：2021-02-17

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