用于腫瘤特異性化療的微生物納米藥物-協(xié)同先天/適應(yīng)性抗腫瘤免疫
雜志名稱：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
作者單位：
中國科學院上海硅酸鹽研究所高性能陶瓷與超微結(jié)構(gòu)國家重點實驗室
中國科學院大學
上海市第十人民醫(yī)院超聲科
同濟大學醫(yī)學院腫瘤中心超聲研究與教育研究所
同濟大學醫(yī)學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，微生物納米醫(yī)學在腫瘤治療領(lǐng)域顯示出巨大的應(yīng)用前景。本文報道了一種新型微生物納米藥物LOD/TPZ@Lips-LA，該藥物通過酰胺縮合反應(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，其中納米藥物通過原位ROS生成和基于LA代謝的TPZ激活誘導腫瘤細胞顯著凋亡，從而引發(fā)強大的免疫原性細胞死亡(ICD)。更重要的是，LOD/TPZ@Lips-LA-induced ICD通過標記的生物標志物表達調(diào)控，誘導腫瘤內(nèi)先天腫瘤相關(guān)巨噬細胞的抗致瘤性M1極化和適應(yīng)性細胞毒性CD8+ T細胞浸潤，從而協(xié)同放大所設(shè)計的微生物藥物的腫瘤抑制作用。這種基于細菌代謝和協(xié)同抗腫瘤免疫的LOD/TPZ@Lips-LA啟用ICD策略，為未來設(shè)計新型微生物納米藥物提供了高效的癌癥治療方法。
