杂志名称：Nano Today
影响因子：17.4
文章题目：Microbiotic nanomedicine for tumor-specific chemotherapy-synergized innate/adaptive antitumor immunity
文献地址：https://doi.org/10.1016/j.nantod.2022.101377
第一作者：
Wencheng Wu, Yinying Pu, Heliang Yao, Han Lin, Jianlin Shi
作者单位：
中国科学院上海硅酸盐研究所高性能陶瓷与超微结构国家重点实验室
中国科学院大学
上海市第十人民医院超声科
同济大学医学院肿瘤中心超声研究与教育研究所
同济大学医学院上海市第十人民医院
引用产品：
Phosphate buffer solution (PBS),
dulbecco's modified eagle medium (DMEM),
calcein, 4, 6-diamidino-2-phenylindole (DAPI),
propidium iodide (PI),
luorescein isothiocyanate (FITC),

cell counting Kit-8 (CCK-8)

文章摘要：
Recently, microbiotic nanomedicine has shown great promise in the field of tumor therapy. In this work, we report a novel microbiotic nanomedicine denoted as LOD/TPZ@Lips-LA, which was constructed by anchoring lactate oxidase (LOD)-and prodrug tirapazamine (TPZ)-coloaded liposomes on the surface of lactobacillus (LA) through amide condensation reaction for chemotherapy-synergized antitumor immunity. TPZ and LOD were efficiently delivered to neoplastic tissue by the tumor-targeting nature of LA, wherein the nanomedicine induced significant tumor cell apoptosis by in situ ROS generation and TPZ activation based on the metabolism of LA, thus evoking robust immunogenic cell death (ICD). More importantly, LOD/TPZ@Lips-LA-induced ICD induces strong anticancer immunity featuring anti-tumorigenic M1 polarization of innate tumor-associated macrophages and infiltration of adaptive cytotoxic CD8+ T cells in tumors by the marked biomarker expression regulations, thereby synergetically amplifying the tumor inhibition effects of the designed microbiotic medicine. Such a strategy of LOD/TPZ@Lips-LA enabled ICD based on bacterial metabolism and synergized antitumor immunity provides a promising paradigm for highly effective cancer therapeutics by designing novel microbiotic nanomedicine in the future.

近年来，微生物纳米医学在肿瘤治疗领域显示出巨大的应用前景。本文报道了一种新型微生物纳米药物LOD/TPZ@Lips-LA，该药物通过酰胺缩合反应将乳酸氧化酶(LOD)和前药替拉帕胺(TPZ)包载脂质体锚定在乳酸菌(LA)表面，用于化疗协同抗肿瘤免疫。利用LA的肿瘤靶向性，TPZ和LOD被有效地传递到肿瘤组织中，其中纳米药物通过原位ROS生成和基于LA代谢的TPZ激活诱导肿瘤细胞显著凋亡，从而引发强大的免疫原性细胞死亡(ICD)。更重要的是，LOD/TPZ@Lips-LA-induced ICD通过标记的生物标志物表达调控，诱导肿瘤内先天肿瘤相关巨噬细胞的抗致瘤性M1极化和适应性细胞毒性CD8+ T细胞浸润，从而协同放大所设计的微生物药物的肿瘤抑制作用。这种基于细菌代谢和协同抗肿瘤免疫的LOD/TPZ@Lips-LA启用ICD策略，为未来设计新型微生物纳米药物提供了高效的癌症治疗方法。