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雜志名稱(chēng)：Nano Today
影響因子：17.4
文章題目：Microbiotic nanomedicine for tumor-specific chemotherapy-synergized innate/adaptive antitumor immunity
文獻(xiàn)地址：https://doi.org/10.1016/j.nantod.2022.101377
作者：Wencheng Wu, Yinying Pu, Heliang Yao, Han Lin, Jianlin Shi
作者單位：中國(guó)科學(xué)院上海硅酸鹽研究所高性能陶瓷與超微結(jié)構(gòu)國(guó)家重點(diǎn)實(shí)驗(yàn)室；中國(guó)科學(xué)院大學(xué)；上海市第十人民醫(yī)院超聲科；同濟(jì)大學(xué)醫(yī)學(xué)院腫瘤中心超聲研究與教育研究所；同濟(jì)大學(xué)醫(yī)學(xué)院上海市第十人民醫(yī)院
引用產(chǎn)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.
近年來(lái)，微生物納米醫(yī)學(xué)在腫瘤治療領(lǐng)域顯示出巨大的應(yīng)用前景。本文報(bào)道了一種新型微生物納米藥物L(fēng)OD/TPZ@Lips-LA，該藥物通過(guò)酰胺縮合反應(yīng)將乳酸氧化酶(LOD)和前藥替拉帕胺(TPZ)包載脂質(zhì)體錨定在乳酸菌(LA)表面，用于化療協(xié)同抗腫瘤免疫。利用LA的腫瘤靶向性，TPZ和LOD被有效地傳遞到腫瘤組織中，其中納米藥物通過(guò)原位ROS生成和基于LA代謝的TPZ激活誘導(dǎo)腫瘤細(xì)胞顯著凋亡，從而引發(fā)強(qiáng)大的免疫原性細(xì)胞死亡(ICD)。更重要的是，LOD/TPZ@Lips-LA-induced ICD通過(guò)標(biāo)記的生物標(biāo)志物表達(dá)調(diào)控，誘導(dǎo)腫瘤內(nèi)先天腫瘤相關(guān)巨噬細(xì)胞的抗致瘤性M1極化和適應(yīng)性細(xì)胞毒性CD8+ T細(xì)胞浸潤(rùn)，從而協(xié)同放大所設(shè)計(jì)的微生物藥物的腫瘤抑制作用。這種基于細(xì)菌代謝和協(xié)同抗腫瘤免疫的LOD/TPZ@Lips-LA啟用ICD策略，為未來(lái)設(shè)計(jì)新型微生物納米藥物提供了高效的癌癥治療方法。