Two-phase releasing immune-stimulating composite orchestrates protection against microbial infections
Two-phase releasing immune-stimulating composite orchestrates protection against microbial infections
复制标题
两相释放免疫刺激复合材料可协调预防微生物感染
DOI：
10.1016/j.biomaterials.2021.121106
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发表时间：
2021
期刊：
影响因子：
14
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Zhao H;Lv XJ;Huang J;Huang SG;Zhou HT;Wang HR;Xu YY;Wang J H;Wang J;Liu Z
脓毒症是一种由各种感染引起的急性器官功能障碍综合征，尽管医疗技术不断发展，但仍有很高的死亡率。本文通过将海藻酸钠（ALG）与胞壁酰二肽（MDP）和单磷酰脂质A（MPLA）的纳米粒制剂混合，开发了一种两相释放免疫刺激复合物，后两者是从所形成的ALG水凝胶中具有不同释放速率的免疫调节剂。所制备的两相释放复合物可通过快速释放MDP增强巨噬细胞的吞噬和杀菌功能，提供瞬时脓毒症保护。随后，这种复合物可以通过持续释放MPLA来持续激活免疫系统，通过调节各种促炎细胞因子的产生，促进巨噬细胞的极化，并增加脓毒症攻击后病变中自然杀伤（NK）细胞的百分比，从而进一步提供长期脓毒症保护。在这种治疗后，小鼠从脓毒症攻击中存活下来，可以抵抗第二次感染。值得注意的是，用我们的复合物治疗可以增加盲肠结扎穿孔（CLP）诱导的多微生物脓毒症模型中的小鼠存活率。这项工作提供了一种易于翻译的免疫刺激制剂，用于在各种触发原因下有效预防脓毒症。我们的策略可能有希望长期广泛预防各种感染，并可能在可靠的疫苗可用之前用于保护新的大流行下的医务工作者。
Sepsis, a syndrome of acute organ dysfunction induced by various infections, could lead to a very high mortality in hospitals despite the development of advanced medical technologies. Herein, a type of two-phase releasing immune-stimulating composite is developed by mixing alginate (ALG) with muramyl dipeptide (MDP) and the nanoparticle formulation of monophosphoryl lipid A (MPLA), the latter two are immunomodulatory agents with different release rates from the formed ALG hydrogel. The obtained two phase-releasing composite could provide instantaneous sepsis protection by the rapid release of MDP to enhance the phagocytic and bactericidal function of macrophages. Later on, such composite could further offer long-term sepsis protection by the sustained release of MPLA to continuously activate the immune system,viaup-regulating the production of various pro-inflammatory cytokines, promoting the polarization of macrophages, and increasing the percent of natural killer (NK) cells in the lesion after sepsis challenge. Mice survived from sepsis challenge after such treatment could resist a second infection. Notably, treatment with our composite could increase the mouse survival rate in a cecal ligation and puncture (CLP) induced polymicrobial sepsis model. This work provides an easy-translatable immune-stimulating formulation for effective protection against sepsis under various triggering causes. Our strategy may be promising for long-term broad prevention against various infections, and could potentially be used to protect medical workers under a new pandemic before a reliable vaccine is available.