In-situ clickable prodrug nanoplatform locally activates T lymphocytes to potentiate cancer immunotherapy
文献类型：期刊论文
| 作者 | Hou, Bo1,2; Ye, Jiayi2,3; Li, Junhao2; Xu, Zhiai1; Yu, Haijun2,3
|
| 刊名 | NANO TODAY
 |
| 出版日期 | 2022-12-01 |
| 卷号 | 47页码:11 |
| ISSN号 | 1748-0132 |
| 关键词 | Immune-excluded tumor Extracellular matrix In-situ click reaction Prodrug nanoparticles Immune resistance |
| DOI | 10.1016/j.nantod.2022.101661 |
| 通讯作者 | Xu, Zhiai(zaxu@ecnu.chem.edu.cn) ; Yu, Haijun(hjyu@simm.ac.cn) |
| 英文摘要 | The immune-excluded tumors (IETs) respond marginally to current immune blockade therapy due to the presence of pathophysiological barriers to restrict intratumoral infiltration of the cytotoxic T lymphocytes (CTLs). In this study, to improve the immunotherapy of the IETs, we proposed an in-situ clickable prodrug nanoplatform composed of two sets of acidity-activatable nanoparticles (NPs) for combinatory treatment. The first set of the NPs, namely precursor NPs, could be activated with the extracellular tumor acidity to label tumor extracellular milieu with dibenzocyclooctyne (DBCO) and indocyanine green, which performed florescence imaging-guided photothermal ablation of the extracellular matrix, thereby recruiting the tumor-infiltrating CTLs. The second set of NPs (i.e., the secondary NPs) were functionalized with azide groups, and specifically accumulated at the tumor site via bioorthogonal click reaction with DBCO. The secondary NPs were deshelled with matrix metalloproteinase-2 and activated in the endocytic acidic mi-croenvironment for intracellular release of the BRD4 inhibitor JQ1. Sequential administration of the pre -cursor and the secondary NPs, effectively promoted intratumoral infiltration of CTLs, suppressed PD-L1 upregulation, and was effective for regression 4T1 breast tumor growth, a model of the IETs. This study utilizing the tumor microenvironment-activatable in-situ click chemistry might provide an unprecedented modality to potentiate immunotherapy of the IETs.(c) 2022 Elsevier Ltd. All rights reserved. |
| WOS关键词 | EXTRACELLULAR-MATRIX ; PD-L1 BLOCKADE ; IMMUNE CELLS ; NANOPARTICLES ; FIBROBLASTS ; RESISTANCE ; EXCLUSION ; INNATE ; STROMA |
| 资助项目 | National Natural Science Foundation of China[U22A20328] ; National Natural Science Foundation of China[51873228] ; National Natural Science Foundation of China[22074043] ; National Natural Science Foundation of China[52111530092] ; International Cooperation Project of Science and Technology Commission of Shanghai Municipality[20430711800] |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCI LTD |
| WOS记录号 | WOS:000895537400001 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/304318]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Xu, Zhiai; Yu, Haijun |
| 作者单位 | 1.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res & Ctr Pharmaceut, Shanghai 201203, Peoples R China 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China |
| 推荐引用方式 GB/T 7714 | Hou, Bo,Ye, Jiayi,Li, Junhao,et al. In-situ clickable prodrug nanoplatform locally activates T lymphocytes to potentiate cancer immunotherapy[J]. NANO TODAY,2022,47:11. |
| APA | Hou, Bo,Ye, Jiayi,Li, Junhao,Xu, Zhiai,&Yu, Haijun.(2022).In-situ clickable prodrug nanoplatform locally activates T lymphocytes to potentiate cancer immunotherapy.NANO TODAY,47,11. |
| MLA | Hou, Bo,et al."In-situ clickable prodrug nanoplatform locally activates T lymphocytes to potentiate cancer immunotherapy".NANO TODAY 47(2022):11. |
入库方式： OAI收割
来源：上海药物研究所
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