Multifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy.
Multifunctional silica nanocomposites prime tumoricidal immunity for efficient cancer immunotherapy.
复制标题
多功能二氧化硅纳米复合材料具有主要的杀肿瘤免疫力，可实现有效的癌症免疫治疗
DOI：
10.1186/s12951-021-01073-2
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发表时间：
2021-10-18
影响因子：
10.2
通讯作者：
Li A
中科院分区：
文献类型：
--
作者：
Yang L;Li F;Cao Y;Liu Q;Jing G;Niu J;Sun F;Qian Y;Wang S;Li A
肿瘤免疫微环境（TIME）是导致肿瘤免疫治疗失败的主要原因，其主要原因是免疫原性差和免疫抑制因子的存在。因此，建立有效的治疗敌对时间重塑有相当大的潜力，以提高免疫反应率持久的肿瘤生长迟缓。本研究旨在开发一种新型的纳米复合材料，聚乙烯亚胺修饰的树枝状介孔二氧化硅纳米颗粒负载microRNA-125 a（DMSN-PEI@ 125 a），以协同增强免疫应答和免疫抑制逆转，最终产生杀肿瘤环境。我们的结果表明，DMSN-PEI@ 125 a在小鼠巨噬细胞和宫颈癌细胞系TC-1的细胞摄取、以协同方式使肿瘤相关巨噬细胞（TAM）复极化为M1型以及促进TC-1免疫原性死亡方面表现出优异的能力。肿瘤内注射DMSN-PEI@ 125 a促进更多损伤相关分子模式的释放，并增强自然杀伤和CD 8 +T细胞的浸润。同时，复极化的TAM可作为一种辅助剂，促进抗肿瘤免疫，从而以协同的方式抑制TC-1小鼠模型中的肿瘤生长。总的来说，这项工作突出了DMSN-PEI@ 125 a在产生炎症TIME和激发抗肿瘤免疫方面的多功能作用，这可能是癌症免疫治疗的潜在药物。
The tumor immune microenvironment (TIME) has been demonstrated to be the main cause of cancer immunotherapy failure in various malignant tumors, due to poor immunogenicity and existence of immunosuppressive factors. Thus, establishing effective treatments for hostile TIME remodeling has considerable potential to enhance immune response rates for durable tumor growth retardation. This study aims to develop a novel nanocomposite, polyethyleneimine-modified dendritic mesoporous silica nanoparticles loaded with microRNA-125a (DMSN-PEI@125a) to synergistically enhance immune response and immunosuppression reversion, ultimately generating a tumoricidal environment. Our results showed that DMSN-PEI@125a exhibited excellent ability in cellular uptake by murine macrophages and the cervical cancer cell line TC-1, repolarization of tumor associated macrophages (TAMs) to M1 type in a synergistic manner, and promotion of TC-1 immunogenic death. Intratumor injection of DMSN-PEI@125a facilitated the release of more damage-related molecular patterns and enhanced the infiltration of natural killer and CD8+T cells. Meanwhile, repolarized TAMs could function as a helper to promote antitumor immunity, thus inhibiting tumor growth in TC-1 mouse models in a collaborative manner. Collectively, this work highlights the multifunctional roles of DMSN-PEI@125a in generating an inflammatory TIME and provoking antitumor immunity, which may serve as a potential agent for cancer immunotherapy.
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DOI：
10.1084/jem.20050915
发表时间：
2005-12-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Casares N;Pequignot MO;Tesniere A;Ghiringhelli F;Roux S;Chaput N;Schmitt E;Hamai A;Hervas-Stubbs S;Obeid M;Coutant F;Métivier D;Pichard E;Aucouturier P;Pierron G;Garrido C;Zitvogel L;Kroemer G
通讯作者：
Kroemer G
影响因子：
82.9
作者：
Binnewies M;Roberts EW;Kersten K;Chan V;Fearon DF;Merad M;Coussens LM;Gabrilovich DI;Ostrand-Rosenberg S;Hedrick CC;Vonderheide RH;Pittet MJ;Jain RK;Zou W;Howcroft TK;Woodhouse EC;Weinberg RA;Krummel MF
通讯作者：
Krummel MF
影响因子：
32.4
作者：
Noy, Roy;Pollard, Jeffrey W.
通讯作者：
Pollard, Jeffrey W.
影响因子：
21.3
作者：
Baer, Caroline;Squadrito, Mario Leonardo;De Palma, Michele
通讯作者：
De Palma, Michele
影响因子：
4.6
作者：
Melton, David W.;Lei, XiuFen;Shireman, Paula K.
通讯作者：
Shireman, Paula K.