Nanovesicles loaded with a TGF-& beta; receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy
文献类型：期刊论文
| 作者 | Zhou, Mengxue1; Wang, Jiaxin1,2; Pan, Jiaxing1; Wang, Hui2; Huang, Lujia1; Hou, Bo1; Lai, Yi1; Wang, Fengyang3; Guan, Qingxiang4; Wang, Feng5 |
| 刊名 | NATURE COMMUNICATIONS
 |
| 出版日期 | 2023-06-16 |
| 卷号 | 14期号:1页码:18 |
| DOI | 10.1038/s41467-023-39035-x |
| 通讯作者 | Yu, Haijun(hjyu@simm.ac.cn) |
| 英文摘要 | Targeting the TGF-& beta; signaling pathway has been exploited to relieve immunosuppression in the tumor microenvironment. Here the authors describe the design of a nanoplatform integrating the TGF-& beta; receptor 1 inhibitor LY2157299 and the ROS-responsive JQ1 pro-drug, promoting anti-tumor immune responses in preclinical cancer models. The immune-excluded tumors (IETs) show limited response to current immunotherapy due to intrinsic and adaptive immune resistance. In this study, it is identified that inhibition of transforming growth factor-& beta; (TGF-& beta;) receptor 1 can relieve tumor fibrosis, thus facilitating the recruitment of tumor-infiltrating T lymphocytes. Subsequently, a nanovesicle is constructed for tumor-specific co-delivery of a TGF-& beta; inhibitor (LY2157299, LY) and the photosensitizer pyropheophorbide a (PPa). The LY-loaded nanovesicles suppress tumor fibrosis to promote intratumoral infiltration of T lymphocytes. Furthermore, PPa chelated with gadolinium ion is capable of fluorescence, photoacoustic and magnetic resonance triple-modal imaging-guided photodynamic therapy, to induce immunogenic death of tumor cells and elicit antitumor immunity in preclinical cancer models in female mice. These nanovesicles are further armored with a lipophilic prodrug of the bromodomain-containing protein 4 inhibitor (i.e., JQ1) to abolish programmed death ligand 1 expression of tumor cells and overcome adaptive immune resistance. This study may pave the way for nanomedicine-based immunotherapy of the IETs. |
| WOS关键词 | ANTITUMOR IMMUNITY ; NANOPARTICLES ; FIBROBLASTS ; MECHANISMS ; BLOOD ; CELLS |
| 资助项目 | National Natural Science Foundation of China[U22A20328] ; National Natural Science Foundation of China[82102915] ; National Natural Science Foundation of China[82203041] ; Science and Technology Commission of Shanghai Municipality[23ZR1475000] ; Science and Technology Commission of Shanghai Municipality[20430711800] ; China Postdoctoral Science Foundation[2021M700157] ; Shanghai Post-Doctoral Excellence Program[2021424] ; Lingang Laboratory[LG-QS-202206-04] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:001018392800013 |
| 出版者 | NATURE PORTFOLIO |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306719]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Yu, Haijun |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China 2.Inner Mongolia Univ, Coll Chem & Chem Engn, Hohhot 010021, Peoples R China 3.Tongji Univ, Shanghai Peoples Hosp 10, Sch Med, Shanghai 200072, Peoples R China 4.Jilin Univ, Sch Pharm, Changchun 130021, Peoples R China 5.Fudan Univ, Huadong Hosp, Shanghai Med Coll, Dept Gastroenterol, Shanghai 200040, Peoples R China 6.East China Normal Univ, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhou, Mengxue,Wang, Jiaxin,Pan, Jiaxing,et al. Nanovesicles loaded with a TGF-& beta; receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy[J]. NATURE COMMUNICATIONS,2023,14(1):18. |
| APA | Zhou, Mengxue.,Wang, Jiaxin.,Pan, Jiaxing.,Wang, Hui.,Huang, Lujia.,...&Yu, Haijun.(2023).Nanovesicles loaded with a TGF-& beta; receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy.NATURE COMMUNICATIONS,14(1),18. |
| MLA | Zhou, Mengxue,et al."Nanovesicles loaded with a TGF-& beta; receptor 1 inhibitor overcome immune resistance to potentiate cancer immunotherapy".NATURE COMMUNICATIONS 14.1(2023):18. |
入库方式： OAI收割
来源：上海药物研究所
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